CPT vs PLA Codes: What Molecular Labs Need to Know

Molecular and genetic tests are some of the highest-value claims a laboratory submits, and some of the most frequently denied. A large share of those denials come down to one question: which code describes the test? For many proprietary tests, the answer is a Proprietary Laboratory Analyses (PLA) code, not a Tier 1 or Tier 2 molecular pathology code.

This guide explains how PLA codes work, when they take priority, and what labs need to do to bill them correctly.

What PLA codes are

PLA codes are a section of the CPT code set maintained by the American Medical Association. Each PLA code describes a single proprietary clinical laboratory test, such as a branded multi-gene panel or an assay offered by one laboratory or manufacturer. PLA codes use four digits followed by the letter U, for example 0001U, and new codes are released quarterly rather than once a year.

How molecular CPT codes are organized

Before choosing a PLA code, it helps to understand where it sits among the other molecular codes:

Tier 1 molecular pathology codes (81105–81383) describe analysis of a specific gene, such as a single gene variant test.
Tier 2 codes (81400–81408) group less common gene tests by technical resource level.
Genomic sequencing procedure codes (81410–81471) cover multi-gene sequencing panels.
Multianalyte assays with algorithmic analyses (MAAA) report tests that combine several results into a score.
Unlisted molecular pathology (81479) is used only when no other code fits.

When to use a PLA code

CPT guidance states that when a PLA code is available to report a given proprietary test, it should be used instead of other CPT codes for that test. In practice, that means checking the PLA code list before assigning a Tier 1, Tier 2, or unlisted code. Billing the individual genes in a test that has its own PLA code is a common cause of denials and payer recoupments.

Build a crosswalk in your LIS that maps each test on your menu to its correct code, including the PLA code where one exists. Review it every quarter when the AMA publishes new PLA codes.

PLA vs Tier 1 and Tier 2 at a glance

	Tier 1 / Tier 2 codes	PLA codes
What it describes	A specific gene or analyte (Tier 1) or a group of procedures by complexity (Tier 2)	One proprietary test offered by a specific lab or manufacturer
Code format	Five digits, 81105–81408	Four digits plus “U”, for example 0001U
Who requests it	Assigned by the AMA CPT Editorial Panel	Requested by the lab or manufacturer that offers the test
Update cycle	Annual CPT release	Quarterly releases
Coding priority	Used when no PLA code describes the test	Reported instead of other codes when it describes the test

How to apply for a PLA code

A laboratory or manufacturer that offers a proprietary test can request its own PLA code. The general process looks like this:

Confirm the test is a proprietary analysis offered by your lab or a single manufacturer.
Submit an application to the AMA with a full description of the test, its methodology, and the analytes measured.
The PLA Technical Advisory Group reviews the application, and the CPT Editorial Panel approves the code.
Once published in a quarterly release, update your LIS, chargemaster, and payer contracts with the new code.

MolDX and Z-code registration

For Medicare claims processed by MACs that participate in the MolDX program, many molecular tests must be registered in the DEX Diagnostics Exchange and assigned a Z-code identifier. The Z-code is reported on the claim alongside the CPT or PLA code. Missing or mismatched Z-codes are a frequent reason molecular claims are denied in MolDX jurisdictions, so confirm registration before billing a new test.

Molecular coding specialist reviewing a test-to-code crosswalk

A test-to-code crosswalk keeps PLA, Tier 1, and Z-code assignments consistent across claims.

How PLA codes are priced

A new code does not guarantee payment. For Medicare, new laboratory codes are priced on the Clinical Laboratory Fee Schedule through crosswalking to an existing code with a similar test, or through gapfilling, where MACs set a rate based on available information. Commercial payers set their own rates and coverage policies, so labs should confirm coverage and negotiate rates for new PLA codes in their contracts.

Common PLA coding mistakes

Billing individual Tier 1 gene codes for a test that has its own PLA code
Using a PLA code for a test the lab does not actually perform as described
Missing a quarterly PLA update and continuing to bill an outdated code
Reporting the PLA code without the required MolDX Z-code
Submitting claims before confirming payer coverage for a newly released code

Key takeaways

PLA codes describe a single proprietary test and use a four-digit plus “U” format.
When a PLA code describes the test, report it instead of Tier 1, Tier 2, or unlisted codes.
PLA codes are released quarterly, so review your code crosswalk every quarter.
Confirm MolDX Z-code registration for Medicare claims in participating jurisdictions.
Verify pricing and coverage before billing a newly released code.

Frequently asked questions

Can any laboratory use a PLA code?

A PLA code describes a specific proprietary test. It should be reported by the lab that performs that test as described in the code, not by labs running a similar but different assay.

What happens if I bill Tier 1 codes for a test with a PLA code?

Payers may deny the claim or later recoup payment, because CPT guidance directs labs to report the PLA code when one describes the test.

How often are PLA codes updated?

The AMA publishes new PLA codes quarterly. Codes become effective on the date listed in each release, so update your LIS and chargemaster as soon as they are published.

Written by

LabMed Billing Editorial Team

Our certified coders and revenue cycle specialists write about the billing problems laboratories face every day, from coding and payer rules to denials and AR.