What Does Signatera Mean?

Signatera is the trade name of a specific blood test made by Natera, Inc., of Austin, Texas. It is not a generic term for a blood test, and it is not interchangeable with other liquid biopsies. If the word appears in your chart, it refers to one product with one manufacturer and one FDA file.

What it measures is circulating tumor DNA, or ctDNA. Cancer cells shed fragments of their DNA into the bloodstream. A test that finds those fragments after surgery is looking for molecular residual disease, usually shortened to MRD, meaning cancer that remains but is too small for any scan to show.

The word that matters in the FDA file is tumor-informed. Signatera is not an off-the-shelf gene panel. It is manufactured for one person.

The sequence runs like this. Your tumor tissue and a matched blood sample both undergo whole exome sequencing, which reads the protein-coding regions of your DNA. Comparing the two shows which mutations belong to the tumor rather than to you. From that list, the lab designs a custom 16-plex primer set, meaning a set of probes aimed at 16 mutations that are specific to your cancer.

After that, each blood draw is tested against your personal 16. Multiplex PCR amplifies those regions from cell-free DNA in plasma, and next-generation sequencing reads them. FDA states the threshold plainly: a result is positive when at least 2 of the 16 variants are detected.

That design has a practical consequence. The test cannot run without tumor tissue. If no usable specimen was saved from your surgery or biopsy, this test cannot be built for you.

On May 15, 2026, FDA granted premarket approval P260004 to Signatera CDx. The CDx stands for companion diagnostic, which is a test formally tied to a treatment decision for a specific drug.

The approved use is narrow. It identifies patients with ctDNA MRD positive status who may benefit from treatment, in muscle invasive bladder cancer, in association with atezolizumab, sold as Tecentriq. The pivotal study behind the approval was IMvigor011.

That is one cancer, one drug, one clinical setting. It does not extend the approval to colorectal cancer, breast cancer, lung cancer, or surveillance in general. If your test was ordered for a different cancer, it was ordered outside the terms of this approval. That is not automatically wrong, but it is a fair thing to ask about, and it changes what evidence stands behind the result.

FDA's summary reports agreement against a comparison method, not accuracy against a cancer diagnosis. The distinction matters.

• Sample-level positive percent agreement was 93.9 percent, and negative percent agreement was 68.4 percent, with no-call samples excluded.
• At the variant level, agreement was 88.8 percent positive and 87.0 percent negative for overlapping variants.
• Analytical sensitivity, described as the limit of detection for the plasma workflow, was a mean variant allele frequency of 0.043 percent. That means roughly 4 tumor DNA molecules in every 10,000.
• Precision testing showed 100 percent sample-level concordance.

Two things to take from that list. The detection floor is genuinely low, which is the point of a bespoke assay. And a percent agreement figure is not the same as your personal chance of having cancer.

These come straight from the approval document, and they are the most useful part of it for a patient.

1. A negative result does not exclude the presence of ctDNA. FDA recommends serial testing, meaning repeated draws over time rather than one snapshot.
2. Sensitivity drops at very low levels, specifically below 0.1 MTM per mL, a count of tumor DNA molecules per milliliter of plasma.
3. It is not for standalone diagnostic use. The result belongs alongside imaging, exam, and pathology, not in place of them.
4. It requires both tumor tissue and a blood sample. No tissue, no test.

There is a fifth thing worth knowing that is implied by the data. Some samples return a no-call rather than a positive or negative. Ask what happened if your report shows no result.

NCI names two FDA-approved liquid biopsy tests in its material on biomarker testing: Guardant360 CDx and FoundationOne Liquid CDx. Those profile mutations in blood to help pick a drug, and they do not need your tumor tissue first.

Signatera answers a different question. It is not asking which drug matches your cancer. It is asking whether any of your cancer is still there.

NCI's tumor marker list includes a third approach, CELLSEARCH, which counts whole circulating tumor cells rather than DNA fragments, and is used in metastatic breast, prostate, and colorectal cancer.

A positive result means tumor DNA was detected in that draw. In the approved bladder cancer setting, that is the finding tied to considering atezolizumab. Outside that setting, a positive result is information, not an automatic instruction to start treatment.

A negative result means none of your 16 variants were found above the detection threshold in that sample. Given FDA's own language, that is reassuring rather than conclusive, which is why serial testing exists.

Neither result replaces your scheduled imaging.

• Was this ordered as the FDA-approved companion diagnostic use, or for another cancer type?
• Which tissue specimen was used to build my personalized panel, and how old is it?
• How many of the 16 variants were detected, and what was the reported level?
• Was this a first result, or part of a series, and when is the next draw?
• If the result is negative, does anything about my imaging or symptoms still worry you?
• If the result is positive, what changes today, and what waits for the next scan?
• What will this cost me, and has coverage been confirmed for my specific cancer?

See Biomarker Testing and Precision Medicine, Pathology Reports, and Imaging Tests.

• https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?ID=P260004
• https://www.accessdata.fda.gov/cdrh_docs/pdf26/P260004B.pdf
• https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment
• https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-list