Alpha-fetoprotein — NCD 121 | CMS Coverage Update

TL;DR: The Centers for Medicare & Medicaid Services modified NCD 121, the National Coverage Determination governing alpha-fetoprotein (AFP) testing, effective March 7, 2026. Here's what billing teams need to know.

CMS AFP coverage policy under NCD 121 covers AFP as a diagnostic laboratory test — specifically as a biochemical marker for monitoring malignancy response to therapy and as a diagnostic tool for hepatocellular carcinoma and germ cell neoplasms. The policy does not list specific CPT or HCPCS codes in the current version. Your billing team needs to verify code assignment against the quarterly Covered Code Lists published by CMS and cross-reference Chapter 120 of the Medicare Claims Processing Manual before submitting claims.

Quick-Reference Table

CMS Alpha-Fetoprotein Coverage Criteria and Medical Necessity Requirements 2026

NCD 121 is the National Coverage Determination that governs whether Medicare covers AFP testing. CMS treats AFP as a diagnostic laboratory test — a polysaccharide marker found in certain carcinomas — and covers it when it serves a specific clinical purpose. Medical necessity is not open-ended here. The policy draws a clear line between what qualifies and what doesn't.

There are two distinct clinical roles AFP plays under this coverage policy. First, AFP supports the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. Second, AFP functions as a non-specific tumor-associated antigen to mark germ cell neoplasms.

For the HCC indication, CMS identifies specific high-risk patient categories. These include patients with alcoholic cirrhosis, cirrhosis of viral etiology, hemochromatosis, and alpha-1 antitrypsin deficiency. AFP testing in these populations also serves to separate patients with benign hepatocellular neoplasms or metastatic disease from those with true HCC. That distinction matters for medical necessity documentation — your clinical notes need to reflect which population the patient falls into.

For germ cell neoplasms, AFP billing is supported when the tumor originates in the testis, ovary, retroperitoneum, or mediastinum. AFP here is acting as a tumor marker to identify and monitor these malignancies. The policy is explicit about the anatomical sites. If the documentation doesn't connect the AFP order to one of those sites, you have a claim denial risk.

The third covered use is monitoring. AFP is effective as a biochemical marker for monitoring the response of certain malignancies to therapy. This is the broadest indication in the policy — and it's the one most likely to support repeat testing on the same patient over time. Your documentation should tie each AFP order to an active treatment course and a specific malignancy being monitored.

Whether AFP testing requires prior authorization under Medicare is not addressed in NCD 121 directly. AFP falls under the Diagnostic Laboratory Tests benefit category, which typically doesn't trigger a prior auth requirement under traditional Medicare. However, Medicare Advantage plans operate differently. If your patients are on Medicare Advantage, check the individual plan's requirements — some MA plans do require prior authorization for tumor markers.

For reimbursement, AFP test claims process under clinical laboratory rules. CMS directs billing teams to Chapter 120 of the Medicare Claims Processing Manual, which covers Clinical Laboratory Services Based on Negotiated Rulemaking. That chapter governs how AFP claims are priced and processed. Pull it and read it — it's not optional guidance.

CMS Alpha-Fetoprotein Exclusions and Non-Covered Indications

NCD 121 doesn't include an explicit experimental or non-covered list. But the structure of the policy creates implied limitations you need to respect.

AFP testing ordered outside the defined high-risk HCC populations — or outside the listed germ cell neoplasm sites — lacks medical necessity support under this NCD. If a claim doesn't connect to alcoholic cirrhosis, viral cirrhosis, hemochromatosis, alpha-1 antitrypsin deficiency, or a germ cell tumor of the testis, ovary, retroperitoneum, or mediastinum, you're outside the covered indications. CMS reviewers and Medicare Administrative Contractors will look at the diagnosis codes on the claim. If those codes don't map to a covered indication, expect scrutiny.

Routine screening AFP in low-risk patients is not supported by this policy. The NCD language is specific about high-risk populations. Ordering AFP broadly without documented risk factors is a documentation gap that creates exposure during audits.

Coverage Indications at a Glance

CMS Alpha-Fetoprotein Billing Guidelines and Action Items 2026

Here's what to do before and after the effective date of March 7, 2026.

CPT, HCPCS, and ICD-10 Codes for Alpha-Fetoprotein Under NCD 121

Covered CPT Codes (When Selection Criteria Are Met)

NCD 121 does not list specific CPT or HCPCS codes in the policy document. CMS publishes AFP-applicable codes in its quarterly Covered Code Lists, which are updated regularly. The policy explicitly directs billing teams to those quarterly lists for current covered codes.

Access the quarterly Covered Code Lists at: https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/Internet-Only-Manuals-IOMs-Items/CMS018912 (Chapter 120 of the Medicare Claims Processing Manual, Clinical Laboratory Services Based on Negotiated Rulemaking).

Do not rely on codes from prior claim submissions or internal charge masters without verifying against the current quarterly list. Code assignments for laboratory tests shift with each quarterly update.

A Note on Local Coverage Determinations

AFP testing may also be subject to local coverage determination rules at the Medicare Administrative Contractor level. MACs can issue LCDs that add specificity to NCD 121 — including additional documentation requirements or coverage restrictions that go beyond the national policy. Check with your regional MAC to see if an active AFP LCD applies to your jurisdiction. If you're not sure which MAC covers your region, your compliance officer or billing consultant can help you find the right one.