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Serum Protein Electrophoresis: A Guide for Myeloma

Medically reviewed by Fatima Sharif, MBBS, FCPS
Written by Joshua Carlucci
Updated on October 2, 2026

Key Takeaways

  • Serum protein electrophoresis, or SPEP, is a blood test that uses an electrical current to separate proteins by size, shape, and charge, and it plays an important role in helping doctors diagnose multiple myeloma.
  • SPEP measures five types of proteins in the blood, and unusual levels can point to conditions like multiple myeloma, lymphoma, liver disease, or inflammation. An M spike, which is a sharp rise in a type of protein called M protein, can be a key sign that doctors look at when exploring a multiple myeloma diagnosis.
  • If you have questions about SPEP results or what they mean for your health, talking with your healthcare team is a great next step, as they will consider your full medical history, symptoms, and other test results to figure out the best path forward.
  • View all takeaways

Wondering how doctors diagnose multiple myeloma? Serum protein electrophoresis (SPEP) is a crucial tool. This simple blood test uses an electrical current to separate blood proteins by size, charge, and shape.

Once an SPEP test separates the proteins into fragments, a process called immunofixation can help to identify the types of immunoglobulins present. Higher levels of certain types of protein fragments may be linked to multiple myeloma or other conditions.

Learning more about SPEP, including how it’s done, what to expect, and how to interpret the results, can help you feel better informed and more in control of what’s happening with your myeloma.

🗳️ How often do you get serum protein electrophoresis (SPEP) testing with multiple myeloma?
Only once so far
Every two to three years
Every year
Every six months or more often

How Does SPEP Work?

Once a healthcare provider draws your blood for an SPEP test, they’ll send it to the lab. To conduct SPEP, a lab specialist uses an electrical current on the blood serum to separate the proteins by size, shape, and electrical charge.

Blood serum is the liquid part of blood that remains after clotting agents are removed. When a person’s blood is brought to the laboratory for analysis, it’s separated into different components, including serum, and different kinds of tests can be run on each component.

Depending on your test results, your doctor may recommend repeating the SPEP test to monitor for changes.

Once the serum proteins have been separated, the specialist usually performs immunofixation electrophoresis (IFE), which helps doctors further understand abnormal protein levels in the blood.

Immunofixation measures unusual proteins in the blood, especially M proteins and antibodies (also known as immunoglobulins), immune system proteins that help fight infections.

Plasma cells produce immunoglobulins, including immunoglobulin G, immunoglobulin A, and immunoglobulin M (IgM), as part of the body’s immune response.

There’s also a urine test available, known as urine protein electrophoresis. We’ll talk more about this test below.

Which Proteins Does SPEP Measure?

SPEP measures levels of five protein types:

  • Albumin
  • Alpha-1 globulin
  • Alpha-2 globulin
  • Beta-globulin
  • Gamma-globulin

Each protein moves at its own speed and groups together when exposed to an electric current, creating specific patterns. As part of the test process, each component is separately measured and compared with normal amounts found in healthy individuals. Patterns are also checked for any differences from normal results.

When Is SPEP Used?

Doctors may order an SPEP test if you show signs of unusual protein levels in the blood that may be linked to multiple myeloma. Some signs and symptoms that may be related to multiple myeloma include:

  • Bone damage — Bone pain or frequent fractures
  • Anemia — Weakness, fatigue, pallor, shortness of breath, and dizziness
  • Hypercalcemia (high calcium levels) — Loss of appetite, increased thirst, constipation, nausea, fatigue, and confusion
  • Kidney damage — Fatigue, swelling, and urinary changes


Frequent infections and unusual bleeding or bruising may also be symptoms. In some cases, a person may show no symptoms. Instead, their healthcare team may first notice a problem when laboratory results indicate high levels of protein in their blood or urine.

A doctor may also notice hypercalcemia in blood test results and order more tests to find the cause.

Other Tests

A test called urine protein electrophoresis might be used if doctors suspect that protein fragments known as light chains or Bence-Jones proteins are being lost in your urine.

If your doctor recommends taking an SPEP test, they’ll likely include the serum free light chain (sFLC) assay test too. This blood test measures the number of light chains in the blood. Levels may be followed over time to assess treatment response.

How Do You Take an SPEP Test?

Preparing for SPEP involves largely the same process as going in for other blood tests and laboratory testing. You may need to temporarily stop taking some medications, depending on your doctor’s advice. You won’t typically have to do anything further before your appointment.

If your SPEP results show elevated levels of certain proteins, doctors may suspect a blood cancer like multiple myeloma or lymphoma, or an inflammatory disease.

A medical professional will take a blood sample, which will then be processed by the laboratory. The lab technicians will measure the amount of each protein and consider the results alongside your other signs and symptoms.

Normal SPEP Results

SPEP results are measured in grams per deciliter (g/dL), although reference ranges may vary. For adults, the typical reference ranges are:

  • Total protein — 6.4 to 8.3 g/dL
  • Albumin — 3.3 to 5.7 g/dL
  • Alpha-1 globulin — 0.1 to 0.4 g/dL
  • Alpha-2 globulin — 0.3 to 0.9 g/dL
  • Beta-globulin — 0.7 to 1.5 g/dL
  • Gamma-globulin — 0.5 to 1.4 g/dL

These SPEP ranges help doctors diagnose conditions like multiple myeloma or decide which tests are needed for further investigation.

What Does a SPEP Test Show in Myeloma?

Your SPEP results give an estimate of how much of each protein fragment is present in your blood. While this doesn’t provide a definitive diagnosis of multiple myeloma, it can give your healthcare team a clearer picture of what’s going on.

Along with your test results, your doctor will consider your symptoms and medical history to determine next steps.

Low Levels

Low levels of total serum protein in an SPEP test could signal the following issues:

  • Malnutrition
  • Nephrotic syndrome (kidneys leak too much protein into the urine)
  • Cirrhosis (scarring of the liver)
  • Liver disease
  • The inability of the digestive system to absorb and process protein

Low beta-globulin can be associated with conditions such as malnutrition or low lipoprotein levels.

What’s an M Spike?

An M spike refers to a sharp increase in the number of monoclonal antibodies (M proteins) in the blood. Myeloma cells make M protein, so an unusually high level may indicate that a person could have multiple myeloma.

For SPEP, an electrical current is used on samples of blood serum to separate different types of proteins by size, shape, and electrical charge.

In cases of elevated protein levels, such as higher gamma-globulin, doctors may suspect a blood cancer like multiple myeloma or lymphoma, or an inflammatory disease. They may also indicate a less serious condition related to myeloma — monoclonal gammopathy of undetermined significance (MGUS).

A higher-than-normal alpha-2 globulin level may point to inflammation.

An increase in beta-fraction globulin and its components (C3, transferrin, and beta-lipoprotein) may be due to hormonal medications or the body’s inability to break down fats.

A spike in gamma-globulin protein may indicate:

  • Blood cancers such as multiple myeloma
  • Liver disease
  • An infection
  • Inflammatory disease

When Is SPEP Repeated?

Depending on your test results, your doctor may recommend repeating the SPEP test to monitor for changes. The International Myeloma Working Group recommends repeating SPEP after six months in people diagnosed with MGUS.

If your initial SPEP results were within a normal range, your doctor may check other lab values, including:

  • Complete blood count (CBC)
  • Kidney function tests
  • Serum calcium levels

People with high risk factors may require SPEP testing every year. Those with low-risk MGUS may require SPEP testing every two to three years. If new symptoms develop, you may need testing more often.

Talk to Your Doctor

Your medical history and any medications you take can affect your SPEP results, so your healthcare team will consider these factors when interpreting the lab values. Although SPEP and IFE tests provide insight into abnormal protein levels, they don’t pinpoint the exact cause.

Depending on your results, your medical team may order additional tests, such as a bone marrow biopsy or other blood tests. Results of these may be needed to confirm a diagnosis or explore other potential causes.

If results suggest multiple myeloma, you may be referred to an oncology specialist.

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A MyMyelomaTeam Member

53 years ago I was drafted in the Army after I was a new Medical Technologist. I was stationed at Walter Reed Hospital in the Immunology Department where we diagnosed Multiple Myeloma and other… read more

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my M spike remains at 0.1. seems to me myeloma is still "lurking ". should I be mildly concerned?

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