When people talk about “the Natera cancer test,” they almost always mean Signatera. Natera, a California genetic testing company, makes several tests, but Signatera is its flagship cancer product. It is not a screening test for healthy people. It is for people who have already been diagnosed with cancer, usually after surgery, to find out whether any cancer was left behind and to catch a recurrence early.
What Signatera Does
Signatera is custom-built for each individual, using circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard tools, and help guide treatment decisions. Doctors call this molecular residual disease, or MRD, testing. businesswire
The test works in two stages. First, Natera sequences a sample of the patient’s removed tumor alongside a normal blood sample. The tumor tissue and matched normal sample go through whole exome sequencing to identify the clonal mutations specific to that patient’s cancer. Natera then builds a personal blood test that tracks those mutations. From then on, each follow-up is a simple blood draw. Some patients report that Natera mails the blood collection vials and will send a phlebotomist to do the draw. excellusbcbsmayoclinic
Results come back as positive or negative, along with a number. Signatera is a quantitative test that reports in mean tumor molecules per milliliter of plasma. A reading of 0.00 means no tumor DNA was found. genomed
How Effective Is It?
The early evidence is strongest in colorectal cancer. In a widely cited 2019 study published in JAMA Oncology, researchers followed 130 patients with stage I to III colorectal cancer in Denmark, analyzing 829 blood samples over time. The test detected recurrence up to 16.5 months earlier than standard imaging, an average of 8.7 months earlier. Serial testing caught 14 of 16 relapses (88 percent sensitivity), and 455 of 456 samples from patients who did not relapse correctly tested negative (99.8 percent specificity). itnonlineitnonline
The study also showed how strongly the result predicts what happens next. Patients who tested positive and did not receive further treatment relapsed in 93 percent of cases, while patients who stayed negative had a relapse rate of 3 percent. medthority
Newer versions are being tested across more cancers. A 2025 study of the newer Signatera Genome version covered 392 patients across breast, lung, melanoma, kidney, and colorectal cancers, and reported overall longitudinal sensitivity of 94 percent and specificity of 100 percent. Keep in mind that much of the published data comes from studies Natera sponsors or co-authors. businesswire
Regulatory and guideline support has grown. In May 2026, the FDA approved Signatera CDx as a companion diagnostic for muscle-invasive bladder cancer, and in June 2026 Japan approved it for colorectal cancer. National Comprehensive Cancer Network guidelines for colon and rectal cancer now list ctDNA as a high risk factor for recurrence after surgery, while remaining cautious about using it for routine surveillance. naterabusinesswire
The Pros
Earlier warning. The test can flag returning cancer months before it shows up on a CT scan, which may open the door to earlier treatment.
Personalized. Because it tracks mutations from your own tumor, it is designed to pick up very small amounts of cancer DNA with very few false positives.
Simple follow-up. After the initial setup, each test is a routine blood draw, often arranged at home.
Possibly fewer scans. One patient on the Mayo Clinic Connect forum said her oncologist used quarterly Signatera results to cut her PET scans from every six months down to once a year, reducing radiation exposure. That is one person’s experience, not a standard practice. mayoclinic
Peace of mind. Many patients find a run of negative results reassuring during the anxious years after treatment.
Broad Medicare coverage. Natera states that Medicare patients with stage II or III colorectal cancer are fully covered, and coverage has since expanded to several other solid tumor types. natera
The Cons
A negative result is not a guarantee. Natera’s own report language states that a negative result does not definitively indicate the absence of cancer. genomed
Weaker in some cancers and locations. The test is expected to have limited sensitivity in GIST, kidney cancers, primary brain tumors, and lymphoma because those tumors shed little DNA into the blood. Independent research has also raised concerns. A City of Hope study found the test missed early colorectal recurrences in the lungs; three patients tested negative while standard imaging found disease. The lead researcher cautioned that it may be premature to base treatment decisions solely on ctDNA results. view example conclusion +2
Unclear what to do with a positive result. A positive test can create stress when scans show nothing. Patients on the Mayo Clinic forum report oncologists telling them it is unclear whether or how to change a treatment plan based on Signatera results. In a later City of Hope series, some patients who turned positive during surveillance later reverted to negative on their own and never recurred. mayocliniconcodaily
Requires tumor tissue. Because the test is built from your tumor, it cannot be used if no tumor tissue is available. Setup also takes time before the first result. mayoclinic
Evidence is still maturing. A UK National Institute for Health and Care Excellence briefing noted there is no prospective evidence yet on how using Signatera in practice changes treatment decisions or outcomes, and experts advised against routine NHS use. Large trials testing that question are underway. nice
Cost and coverage gaps. NICE listed the test at roughly £2,900 to £3,500 per test. In the US, Natera’s average selling price per Signatera test was about $1,275 in mid-2026. Coverage outside Medicare is uneven; some major commercial insurers have listed Signatera as experimental. Natera offers financial assistance, a cash pay rate, and a compassionate care option, and its billing line is 1-844-384-2996. http://www.nice.org.uk +4
Alternatives to Signatera
Other MRD blood tests. Signatera is the best-known option, but competitors exist. Breastcancer.org lists Guardant Reveal, Precise MRD, NeXT Personal Dx, and Haystack MRD as other MRD tests. The biggest difference is whether a test is tumor-informed or tumor-naive. Guardant Reveal does not require tumor tissue, so it can be used for MRD testing when tissue is unavailable. NeXT Personal Dx from Personalis takes the opposite approach; it is tumor-informed and uses whole-genome sequencing rather than the exome or targeted sequencing used by most competitors. Natera itself offers Latitude, a tumor-naive MRD test, for patients without usable tissue. Be wary of marketing comparisons between these tests; Guardant has sued Natera, arguing that comparing studies with different methods and patient groups cannot prove one test is superior. Signatera and Other MRD Tests for Breast Cancer +4
Traditional tumor marker blood tests. Depending on the cancer, doctors may track markers such as CEA for colorectal cancer, CA 15-3 or CA 27.29 for breast cancer, CA 19-9 for pancreatic cancer, or PSA for prostate cancer. They are inexpensive and widely covered, but generally less sensitive and less specific than MRD testing.
Imaging. CT, PET, MRI, and ultrasound remain the backbone of follow-up care and are what most guidelines still rely on. Many oncologists who use Signatera use it alongside imaging rather than instead of it.
Standard surveillance schedules. Regular office visits, physical exams, and cancer-specific checks such as colonoscopy follow published guidelines and remain the baseline every patient should receive.
Multi-cancer early detection tests. Tests like Galleri are designed for people without a cancer diagnosis and serve a different purpose. They are not a substitute for MRD monitoring after treatment.
Who Should Consider It
Signatera makes the most sense for people who have had surgery for a solid tumor, especially stage II or III colorectal cancer, bladder cancer, or another type where Medicare or their insurer covers it, and whose oncologist has a plan for how results will be used. The key question to ask your doctor is simple: what will we do differently if this test comes back positive, or negative? If there is no clear answer, the test may add anxiety without adding much benefit.
The Bottom Line
Signatera is a genuinely useful tool that can spot returning cancer earlier than scans in many patients, and its role in cancer care is expanding quickly. It is not perfect, it works better for some cancers than others, and the research on whether acting on its results improves survival is still coming in. Treat it as one piece of a follow-up plan built with your oncologist, not a replacement for imaging and standard care.
This article is for general information only and is not medical advice. Talk with your oncologist about whether MRD testing fits your situation.
Sources:
MarketBeat: Natera Q2 2026 earnings highlights
Natera: IVDR certification for Signatera
Medthority: Signatera JAMA Oncology study
Business Wire: Signatera Genome at ASCO 2025
Business Wire: NCCN ctDNA guidance
Business Wire: City of Hope study on Signatera limitations
OncoDaily: Marwan Fakih surveillance series
NICE: Signatera briefing
Natera: Oncology billing
Natera: Insurance coverage PDF
Breastcancer.org: Signatera and other MRD tests
Excellus BCBS: MRD testing policy
GenomeWeb: Guardant sues Natera
GenomeWeb: NeXT Personal TRACERx data
Mayo Clinic Connect: Signatera discussion