M protein is an abnormal protein made by cancerous myeloma cells. The “M” technically stands for monoclonal, but M protein is often referred to as myeloma protein.

High amounts of M protein in the blood or urine can be a sign of multiple myeloma. However, M protein can also occur in other plasma cell disorders, such as monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM). These conditions can sometimes develop into multiple myeloma.

In this article, we’ll explain what M protein is, how it’s measured, and how your care team uses changes in M protein to monitor myeloma.

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What Do High Levels of M Protein Mean?

High M protein levels are a sign that a person has abnormal plasma cells. M protein can be a sign of several different types of diseases. Tests that measure M protein may be used to determine:

• Initial diagnosis
• Whether the condition is getting worse
• How well treatments are working

Diagnosing Multiple Myeloma

Having M protein in your system may be a sign of multiple myeloma. Most people with myeloma have M protein in their blood or urine. If you have M protein, your healthcare provider will likely recommend other tests before making a diagnosis of multiple myeloma. These tests may include:

• Imaging tests
• Genetic tests
• Bone marrow biopsies (when doctors take a sample of the soft tissue from inside your bones)
• Other blood tests

Not everyone with multiple myeloma will have measurable M protein in their blood or urine. In people with light-chain myeloma, the plasma cells produce fragments of proteins instead of whole ones.

In those with nonsecretory myeloma, plasma cells may produce M protein but fail to release it, or they may not produce M protein at all. In such cases, M proteins are not detectable in blood or urine, so diagnosis relies on other tests, including a bone marrow biopsy.

Diagnosing Other Diseases Using M Protein

Finding M protein in the blood or urine does not necessarily mean a person has multiple myeloma. There are several other plasma cell disorders that may also result in high levels of M protein.

Lower levels of M protein may mean a person has a disorder called monoclonal gammopathy of undetermined significance. This condition occurs when there are small numbers of abnormal plasma cells in the bone marrow.

People with MGUS don’t have any signs or symptoms of multiple myeloma, but they have a slightly increased risk of developing it. Each year, about 1 percent of people with MGUS develop a type of cancer.

MGUS can also sometimes lead to other diseases such as plasma cell leukemia, Waldenström macroglobulinemia, or amyloidosis. MGUS is less likely to progress to myeloma than smoldering multiple myeloma.

People with SMM, also called asymptomatic myeloma, have increased levels of monoclonal plasma cells and M protein but don’t have any other myeloma symptoms. An older study estimated the following yearly risks of progression to active multiple myeloma among people with SMM:

• 10 percent per year for the first five years
• 3 percent for the next five years
• 1.5 percent each year after that

Many people with SMM don’t need treatment right away. However, early treatment may benefit some people with high-risk SMM. One study found that people with high-risk SMM who met three specific risk criteria had a 76 percent progression rate over five years. As of November 2025, the U.S. Food and Drug Administration (FDA) has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) for adults with high-risk SMM.

If an M protein test reveals that you have a condition like SMM or MGUS, you can take steps to protect your health. Knowing you’re at risk for developing a condition like myeloma can help you catch it early. People with SMM or MGUS should have regular follow-up visits and tests. If the condition transforms into myeloma, it can be found and treated right away, which may lead to a better outcome.

M Protein in Monitoring Diseases and Treatments

After a condition is diagnosed, doctors may rely on M protein levels to track disease progression and treatment success. M protein levels were used to help stage myeloma in the past.

Healthcare providers most commonly use the Revised International Staging System (R-ISS) for multiple myeloma staging. The Second Revision of the International Staging System (R2-ISS) is also increasingly used to stage multiple myeloma. The older classification system, the Durie-Salmon Staging System, used M protein levels to determine stage.

Healthcare providers often continue measuring M protein levels after diagnosis so they can see when a disease is getting worse. For example, M protein levels may indicate when SMM or MGUS has transformed into myeloma. M protein levels can also help show whether myeloma is becoming more advanced, which may indicate that a person’s treatment plan should change.

M protein levels can also show whether myeloma treatments are working. With a strong treatment response, M protein may become undetectable. Your healthcare team will use several tests to determine your treatment response.

How Is M Protein Measured?

Some tests measure M protein levels while others analyze the M protein type. It’s important to know which type of M protein your plasma cells make.

Antibodies, including M proteins, are made up of two different types of proteins. Each antibody contains two heavy-chain proteins and two light-chain proteins. There are five different types of heavy chains:

• Immunoglobulin G (IgG)
• IgA
• IgM
• IgD
• IgE

Determining which type of M protein (according to its heavy-chain and light-chain proteins) is in your blood or urine can help your healthcare team diagnose specific conditions.

For example, about half of people with multiple myeloma have the IgG type of M protein. The second largest group has IgA. Most of the time, IgM proteins are a sign of Waldenström macroglobulinemia.

Blood Tests

Some tests measure M proteins from blood samples. One such test is serum protein electrophoresis (SPEP). This test separates the proteins within a sample based on their electrical charges. SPEP shows changes in the levels of both M protein and other normal proteins. It reports the overall levels of M protein, but it doesn’t show what type of M protein a person has.

Immunofixation electrophoresis (IFE) tests may be performed along with an SPEP test. IFE tests show what type of M protein a person has, but they don’t show the overall levels.

Blood tests may also include a quantitative immunoglobulins test. This test can measure the levels of IgG, IgA, and IgM.

Another M protein blood test is a serum free light chain (SFLC) assay. Although antibodies are made from both heavy-chain and light-chain proteins, plasma cells usually make more light-chain proteins.

The extra light chains that aren’t used to make antibodies are released into the blood. The SFLC assay measures these blood proteins and can help to diagnose light-chain multiple myeloma.

Urine Tests

The urine protein electrophoresis (UPEP) test measures M protein in urine. It can also detect free light chains, called Bence-Jones proteins.

UPEP usually requires a 24-hour urine sample, meaning you collect all your urine over 24 hours.