Tumor Markers: What Cancer Blood Tests Can and Cannot Say

A tumor marker, in the National Cancer Institute's definition, is anything present in or produced by cancer cells or by other cells of the body in response to cancer or certain benign (noncancerous) conditions that provides information about a cancer (NCI tumor markers fact sheet). Traditionally these have been proteins or other substances made in larger amounts by cancer cells than by normal cells, measured in blood, urine, stool, tumor tissue or other body fluids; increasingly, genomic markers are used as well.

MedlinePlus describes tumor marker tests as most often used after a cancer has been diagnosed: together with other tests they help stage the cancer, estimate prognosis, choose treatment, monitor whether treatment is working and find cancer that remains or returns. Their role in screening people without symptoms is limited, and a raised result cannot by itself diagnose cancer (MedlinePlus: Tumor Marker Tests). This page sets out what the research and the guideline bodies report for the commonly measured markers.

Table of Contents

  1. What a Tumor Marker Is
  2. Why These Are Not Screening Tests
  3. The Markers One by One
  4. What Tumor Markers Are Used For
  5. Reading a Mildly Elevated Result
  6. The New Generation: ctDNA and Liquid Biopsy
  7. When Several Markers Are Measured Together
  8. Lab Differences and Access
  9. Living With Surveillance
  10. Key Research Papers
  11. Connections
  12. Featured Videos

What a Tumor Marker Is

Some tumor markers are linked with only one type of cancer and others with many. The same two limits come up in every source: conditions that are not cancer can raise many markers, and not everyone with a given cancer has a raised level of the marker linked to it. For that reason, the NCI notes, tumor marker measurements are usually combined with other tests, such as biopsies or imaging, to diagnose cancer.

MedlinePlus lists the noncancerous causes for each marker. Examples:

A normal result does not rule cancer out either: MedlinePlus notes, for example, that CA-125 can be low in early ovarian cancer and that some people with liver, ovarian or testicular cancer have normal AFP levels.

Reference ranges vary by laboratory and assay. MedlinePlus explains that labs often use different testing methods and therefore different reference ranges, that a result has to be compared with the range printed on the report that carries it, and that results from different labs cannot be compared directly. Its CEA, CA 19-9 and thyroglobulin pages add that the test method can affect the result, so serial tests are usually done the same way and in the same lab (MedlinePlus: How to Understand Your Lab Results). For that reason this page gives a numerical cut-off only where a cited study states the one it used.

Why These Are Not Screening Tests

A screening test looks for disease in people without symptoms. The NCI summarises the research on circulating tumor markers this way: studies of whether they can be used to screen for cancer have generally found that they do not work well, because they often miss people who have the disease (they are not sensitive enough) or point to cancer in people who do not have it (they are not specific enough).

CA-125 shows both problems. In the 1983 study that introduced the serum assay, 1% of 888 apparently healthy people and 6% of 143 patients with nonmalignant disease had CA-125 above 35 U/mL, against 82% (83 of 101) of patients with surgically demonstrated ovarian carcinoma (Bast 1983). In the first four annual screening rounds of the PLCO trial, 1.4–1.8% of CA-125 tests were positive in each round; the positive predictive value of the combined CA-125 and ultrasound screen was 1.0–1.3% per round, there were 19.5 surgeries for every screen-detected cancer, and 72% of screen-detected cancers were already late stage (III/IV) (Partridge 2009).

Two large randomised trials then measured deaths from ovarian cancer:

The UKCTOCS result shows that finding cancers at an earlier stage did not by itself lower deaths, which is why the trial's authors stressed cancer mortality as the outcome that screening trials need to measure. The US Preventive Services Task Force's 2018 statement found adequate evidence that ovarian cancer screening does not reduce ovarian cancer mortality and that its harms, including unnecessary surgery in women without cancer, are at least moderate; it recommends against screening asymptomatic women who are not known to have a high-risk hereditary cancer syndrome (a D recommendation) (USPSTF 2018, ovarian).

The same limits are written into the MedlinePlus descriptions of other markers: CEA tests are not used to screen for or diagnose cancer, and CA 19-9 and AFP results are not used alone to screen for or diagnose cancer.

Settings where a marker has been studied or recommended for detection:

The Markers One by One

For each marker: what cancer it is used with, what else raises it, and what its known blind spots are. Reference ranges are set by each laboratory for its own assay (see above), so the range printed on a lab report is the one that applies to that result.

PSA (prostate-specific antigen) — prostate

PSA is a protein made by the prostate. MedlinePlus states that there is no specific normal or abnormal level for PSA in blood: in general, the higher the level the more likely cancer is, but a high PSA can occur without prostate cancer and a low PSA with it, and because PSA levels go up and down a raised result is often repeated. The NCI lists PSA for help in diagnosis, assessing response to treatment and looking for recurrence, and the NACB guidelines list it for detecting recurrence and monitoring therapy (Sturgeon 2008). The benign causes are listed above. Full details are on the PSA Test page.

CEA (carcinoembryonic antigen) — colorectal and others

CEA's main documented job is in colorectal cancer. The 2006 ASCO guideline update recommends CEA before surgery if it would help staging and surgical planning, and CEA every 3 months after surgery for stage II and III disease for at least 3 years if the patient is a potential candidate for surgery or chemotherapy of metastatic disease; it calls CEA the marker of choice for monitoring the response of metastatic disease to systemic therapy (Locker 2006). MedlinePlus lists cancers of the colon and rectum, prostate, ovary, lung, thyroid, liver, pancreas and breast as possible causes of high CEA, which is one reason a raised CEA cannot show where a cancer is. Smoking and the benign conditions listed above also raise it, and MedlinePlus states that CEA tests are not used to screen for or diagnose cancer. See the CEA Test page.

CA-125 — ovarian

The 1983 study that introduced the serum assay used 35 U/mL as its upper limit, and rising or falling CA-125 matched progression or regression of epithelial ovarian cancer in 42 of 45 instances (93%) (Bast 1983). The NACB guidelines recommend CA-125 for the differential diagnosis of suspicious pelvic masses in postmenopausal women and for detecting recurrence, monitoring therapy and determining prognosis in ovarian cancer (Sturgeon 2008). As a screen in women at average risk it has not reduced deaths, as the trials above show. The benign causes are listed above. The dedicated CA-125 page covers it in depth, including the ROMA score for a pelvic mass.

CA 19-9 — pancreatic and biliary

MedlinePlus lists cancers of the pancreas, bile duct, colon and rectum, stomach, ovaries and bladder as possible causes of high CA 19-9, and gallstones blocking the bile ducts, cholangitis, pancreatitis, cirrhosis and other liver and bile-duct disease among the non-cancer causes; healthy people can also have high levels. For this reason a CA 19-9 result is not used alone to screen for or diagnose cancer. The 2006 ASCO update states that CA 19-9 can be measured every 1 to 3 months in patients with locally advanced or metastatic pancreatic cancer receiving active therapy, and that rising serial values suggest progression but need confirmation with other studies (Locker 2006).

People who do not make CA 19-9. MedlinePlus notes that some people do not make CA 19-9 even when they have a cancer that usually produces high levels, so for them the test is not useful. CA 19-9 is a Lewis blood-group antigen: in a study of 316 Chinese participants, 9.8% had the Lewis-negative phenotype, serum CA 19-9 levels differed by phenotype, and the authors noted that these gene variants differ between populations (Guo 2017). A normal CA 19-9 therefore does not rule the disease out.

AFP (alpha-fetoprotein) — liver and germ cell

AFP is a protein made by the liver; levels are high in a fetus and drop very low after birth. MedlinePlus lists high AFP as a possible sign of hepatocellular carcinoma, ovarian germ cell tumors and nonseminomatous germ cell tumors of the testicles, and of noncancerous liver conditions (listed above); outside pregnancy, healthy children and adults have very little AFP in their blood. In people at high risk of liver cancer, AFP is used together with ultrasound for surveillance (see above). The AASLD guidance states that in at-risk patients with cirrhosis or chronic hepatitis B, the diagnosis of hepatocellular carcinoma is based on noninvasive imaging criteria and/or pathology (Singal 2023). For testicular cancer, the NACB guidelines recommend AFP, hCG and LDH for diagnosis, staging, prognosis, recurrence detection and therapy monitoring, and AFP to help tell nonseminomatous from seminomatous germ cell tumors (Sturgeon 2008). See the AFP Test page.

Beta-hCG — germ cell tumors and pregnancy

hCG is the hormone that pregnancy tests measure. The NCI lists beta-hCG as a marker for choriocarcinoma and germ cell tumors, used to assess stage, prognosis and response to treatment, and it is one of the three testicular-cancer markers in the NACB guidelines (Sturgeon 2008).

A documented laboratory pitfall is "phantom hCG": persistent low hCG readings produced by a substance that interferes with the test rather than by true hCG. Cole described three such cases, two of them treated with chemotherapy for presumed choriocarcinoma; in each, hCG was found in serum but not in urine, and in the first two, serum values did not fall in step when the sample was diluted (Cole 1998). In a series of 12 women diagnosed with postgestational choriocarcinoma on the basis of persistently positive hCG results, all 12 met the criteria for false-positive hCG, most had undergone needless surgery or chemotherapy, and the assay behaviour pointed to heterophilic antibodies. The authors called for diagnostic protocols to include a compulsory urine hCG test (Rotmensch 2000). Details are on the Beta-hCG page.

CA 15-3 and CA 27.29 — breast

MedlinePlus lists CA 15-3 and CA 27-29 as markers used to monitor treatment in people with advanced breast cancer, and the NACB guidelines state that they, or CEA, may be used for therapy monitoring in advanced disease (Sturgeon 2008). For routine follow-up after primary treatment of breast cancer, the 2013 ASCO guideline update states that tumor markers (CEA, CA 15-3 and CA 27.29), like routine blood counts, chemistry panels and scans, are not recommended in a patient with no symptoms and no specific findings on clinical examination; it recommends regular history, physical examination and mammography (Khatcheressian 2013).

Chromogranin A — neuroendocrine tumors

The NCI lists chromogranin A for help in diagnosing neuroendocrine tumors, assessing treatment response and evaluating recurrence. A common non-cancer cause of a raised level is proton-pump inhibitor (PPI) use. In a records study of 238 patients with raised chromogranin A at three hospitals, 132 were taking PPIs, and 57 of those did not have a neuroendocrine tumor. In 9 of the 57 no medical cause was found; somatostatin receptor imaging was ordered in 4 of them and was normal, and in 6 a repeat measurement after the PPI was stopped was normal. The authors concluded that PPI use can cause unnecessary diagnostic work-up (van Balveren 2022). A 2025 review lists chronic atrophic gastritis, PPI use and inflammatory bowel disease among the gastrointestinal conditions that can raise chromogranin A without any cancer (Romano 2025).

Thyroglobulin — thyroid, after surgery

Thyroglobulin is made by the thyroid, and several thyroid conditions change its level, so MedlinePlus notes that it is not used to diagnose cancer. Its use is after treatment for thyroid cancer: because treatment usually aims to remove all thyroid tissue, there is little or no thyroglobulin in the blood after successful treatment, and a level that stays high or rises again may mean residual or recurrent cancer. MedlinePlus adds that thyroglobulin antibodies attach to thyroglobulin and can make its level appear lower than it is. In one study, these antibodies were present in 25% of patients with differentiated thyroid cancer and 10% of the general population; antibody interference was found in 69% of antibody-positive samples, immunometric assays tended to underestimate thyroglobulin, and serial antibody levels tracked the disease, so the authors proposed the antibody level itself as an additional marker in these patients (Spencer 1998). Broader thyroid blood work is covered on the Thyroid Panel page.

LDH and beta-2 microglobulin — lymphoma and myeloma context

Neither marker is specific to cancer, yet both appear in cancer staging. LDH (lactate dehydrogenase) is listed by the NCI for germ cell tumors, lymphoma, leukemia, melanoma and neuroblastoma, to assess stage, prognosis and response to treatment. In aggressive non-Hodgkin lymphoma, the International Prognostic Index built from 2,031 patients uses age, tumor stage, serum LDH, performance status and the number of extranodal sites to define four risk groups, with predicted five-year survival of 73%, 51%, 43% and 26% (International Non-Hodgkin's Lymphoma Prognostic Factors Project 1993). In testicular cancer, LDH is one of the three serum markers in the NACB guidelines, with AFP and hCG (Sturgeon 2008).

Beta-2 microglobulin is a small protein on the surface of most cells that the kidneys normally filter from the blood. MedlinePlus lists multiple myeloma, chronic lymphocytic leukemia and certain lymphomas as causes of high levels, and kidney disease, autoimmune disorders, HIV and multiple sclerosis among the non-cancer causes. In multiple myeloma, the International Staging System derived from 10,750 patients defines stage I as serum beta-2 microglobulin below 3.5 mg/L with serum albumin of 3.5 g/dL or more (median survival 62 months) and stage III as beta-2 microglobulin of 5.5 mg/L or more (median survival 29 months) (Greipp 2005).

What Tumor Markers Are Used For

In a person with a diagnosed cancer that produces a marker, the marker can be measured repeatedly from a blood sample. The NCI and MedlinePlus describe three main uses:

  1. Tracking treatment response. Serial measurements during treatment can show whether a tumor is responding: falling levels usually mean treatment is helping, and levels that rise or stay high may mean it is not. In the 1983 CA-125 study, changes in the marker matched the course of ovarian cancer in 42 of 45 instances (Bast 1983).
  2. Staging and prognosis at diagnosis. Pre-treatment levels feed into staging and risk systems: LDH in the International Prognostic Index for lymphoma, beta-2 microglobulin in the myeloma staging system, and AFP, hCG and LDH in testicular cancer (see above).
  3. Recurrence surveillance. Measuring markers periodically after treatment is used to check for recurrence. Whether earlier detection changes outcomes has been tested in trials. In the FACS trial of 1,202 people after curative surgery for colorectal cancer, recurrence was treated with curative intent in 6.7% of the CEA-only group, 8% of the CT group and 6.6% of the CEA plus CT group, against 2.3% with minimum follow-up. Deaths did not differ significantly between the intensive groups combined (18.2%) and minimum follow-up (15.9%), and the authors wrote that any survival advantage is likely to be small (Primrose 2014). For early breast cancer, ASCO does not recommend routine tumor markers in follow-up of patients without symptoms (Khatcheressian 2013).

Reading a Mildly Elevated Result

A result a little above the reference range is a common situation. Several points from the reference sources apply:

MedlinePlus also describes what a raised result can lead to: further tests, such as imaging and, for many cancers, a biopsy, which is usually needed to diagnose or rule out cancer.

The New Generation: ctDNA and Liquid Biopsy

Tumors shed cells and fragments of DNA into the blood, and tests that measure them are called liquid biopsies. The NCI's list of tumor markers in common use already includes blood-based genomic tests used as companion diagnostics to select targeted therapies in solid tumors (NCI: Tumor Markers in Common Use).

Multi-cancer early detection (MCED) tests aim to detect many cancers in people without symptoms. The NCI notes that many such tests are in development and several are already marketed, that much remains to be learned about their benefits and harms, and that a critical question is whether treating the cancers they find would reduce deaths from those cancers. What has been published for one methylation-based MCED test:

The CA-125 trials above are the background to the NCI's question: in UKCTOCS, a shift towards earlier-stage disease did not translate into fewer deaths (Menon 2021).

When Several Markers Are Measured Together

The sources above describe several settings in which markers are measured as part of a diagnostic or staging work-up rather than as a screen of healthy people:

MedlinePlus describes the limited screening role of tumor markers as mostly for people at high risk of the cancer linked to the marker (for example because of family history) or with symptoms that could be from that cancer. For ovarian cancer it lists inherited changes in the BRCA1 or BRCA2 genes and Lynch syndrome among the factors that raise risk.

Lab Differences and Access

Living With Surveillance

For people after cancer treatment, surveillance means repeated blood tests over months or years. MedlinePlus describes medical test anxiety, a fear of medical tests that is usually mild but can become a phobia with physical symptoms such as a rapid heartbeat, shortness of breath and trembling. It notes that understanding why a test was ordered, what to expect and what the clinician hopes to learn from the results may reduce some of that anxiety, and lists relaxation techniques such as slow breathing, counting, imagery and muscle relaxation (MedlinePlus: How to Cope with Medical Test Anxiety).

Points from the sources above that bear on surveillance:

Across these sources the documented strength of tumor markers is narrow: following a known cancer through treatment and afterwards. As screens in people without symptoms they have generally not worked well (NCI), and in the ovarian-cancer trials CA-125-based screening did not reduce deaths. Decisions about which tests to have belong with a clinician.

Key Research Papers

Key peer-reviewed sources for the claims on this page — the major screening trials (PLCO, UKCTOCS, ERSPC), the tumor-marker practice guidelines, the CEA-surveillance randomized trial, the AFP-surveillance meta-analysis, and the multi-cancer early-detection literature. Each citation links to the publisher's full record via DOI.

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PubMed Topic Searches

  1. PubMed: CA 19-9 and Lewis-antigen-negative pancreatic cancer
  2. PubMed: Multi-cancer early detection and ctDNA screening
  3. PubMed: Chromogranin A and proton-pump-inhibitor interference
  4. PubMed: Tumor-marker surveillance in asymptomatic breast cancer survivors

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