Blood Test Guide

Serum Protein Electrophoresis (SPEP)

Name: Serum Protein Electrophoresis (SPEP): What It Tests
Creator: Suman Konda
Published: 2026-07-05

SPEP separates blood proteins into bands to detect abnormal proteins. It is the key test for diagnosing multiple myeloma and related blood protein disorders.

Written and clinically reviewed by Suman Konda, PharmD, Clinical Pharmacist · Based on peer-reviewed sources · Editorial policy · Not medical advice

Last reviewed and updated: 01 August 2026 · How we check our content

SPEP normal protein fractions

Protein band	Normal range	What it represents
Total protein	6.3–8.2 g/dL	All serum proteins combined
Albumin	3.5–5.0 g/dL (60% of total)	Liver-made transport protein
Alpha-1 globulin	0.1–0.3 g/dL	Includes alpha-1 antitrypsin
Alpha-2 globulin	0.6–1.0 g/dL	Includes haptoglobin, ceruloplasmin
Beta globulin	0.7–1.2 g/dL	Includes transferrin, complement
Gamma globulin	0.7–1.6 g/dL	Immunoglobulins (antibodies)

What is an M-spike?

Monoclonal protein: a key finding

An M-spike (M-protein or paraprotein) is a tall, narrow spike in the gamma region caused by a single clone of plasma cells producing identical antibody molecules. It is the hallmark finding in multiple myeloma, MGUS (monoclonal gammopathy of undetermined significance), and Waldenström's macroglobulinaemia. MGUS is the most common cause, present in ~3% of people over 50, and requires monitoring but is not cancer. A full workup (serum immunofixation, urine Bence Jones protein, bone marrow biopsy) is needed to distinguish MGUS from myeloma.

Abnormal SPEP patterns

Pattern	Likely diagnosis
M-spike in gamma region	MGUS, myeloma, lymphoma
Low gamma globulins	Immunodeficiency, protein loss
Raised polyclonal gamma	Chronic infection, liver disease, autoimmune disease
Low albumin	Malnutrition, liver disease, nephrotic syndrome

Questions to ask your doctor

Is there an M-spike on my SPEP?
Do I need immunofixation to identify the type of protein?
Could this be myeloma or MGUS?
How often should MGUS be monitored?

Frequently Asked Questions

What is serum protein electrophoresis used for?

It separates blood proteins into bands to detect abnormal patterns: most importantly a 'monoclonal band' (paraprotein) that can indicate myeloma or the pre-cancerous condition MGUS.

What does a paraprotein on electrophoresis mean?

It signals an abnormal clone of plasma cells. Further tests (free light chains, bone marrow biopsy, imaging) then determine whether it's harmless MGUS or a condition like multiple myeloma needing treatment.

Is this the same as a total protein test?

No. Total protein just measures the overall amount, while electrophoresis breaks it down into components, revealing patterns a total protein level would miss.

What the test can and cannot settle

Serum protein electrophoresis separates blood proteins by size and charge, producing a pattern rather than a single number. Its main purpose is detecting a monoclonal band, the M-spike, reflecting a single clone of plasma cells producing identical immunoglobulin. What it cannot do is tell you what that clone means. The same finding spans monoclonal gammopathy of undetermined significance, common with age and mostly harmless, through smouldering myeloma, to active myeloma requiring treatment. Distinguishing these needs the clinical picture, blood counts, calcium, kidney function and imaging, not the electrophoresis alone.

Tests usually run alongside it

Immunofixation, which identifies exactly which heavy and light chain the band contains and is more sensitive for small bands.
Serum free light chain assay, essential because some myelomas produce light chains only and show no M-spike on standard electrophoresis.
Urine electrophoresis for Bence Jones protein, historically the classic test for light chain disease.
Full blood count, calcium, creatinine and albumin, which together identify the organ damage defining active disease.

Reading the other patterns

Not every abnormal electrophoresis involves an M-spike. A diffuse, broad-based increase in the gamma region is polyclonal, reflecting chronic infection, autoimmune disease or liver disease, and is not a marker of malignancy. A reduced gamma fraction suggests immune deficiency, whether inherited, drug-induced or secondary to a haematological condition. Low albumin with raised alpha-2 is the pattern of an acute phase response or nephrotic syndrome. A missing alpha-1 band raises alpha-1 antitrypsin deficiency, worth recognising because it affects both lung and liver.

What follows an incidental M-spike

Most small bands found incidentally in well people prove to be MGUS, which carries a low annual risk of progression and is managed by periodic monitoring rather than treatment. The band size, immunoglobulin type and free light chain ratio together set how closely monitoring is scheduled. Because the finding is common and usually stable, discovering an M-spike is not in itself cause for alarm, but it does need proper characterisation rather than being left unexplained.

MGUS: quantifying the risk of progression

The word "precancerous" is alarming in proportion to the actual risk, which is why numerical framing matters. A landmark long-term follow-up study enrolled 1,384 individuals with MGUS and followed them for a median of 34.7 years; the cumulative probability of progression to multiple myeloma or a related malignancy was approximately 1% per year, translating to roughly 10% at 10 years.² Several features predict a higher trajectory: band size above 15 g/L, abnormal serum free light chain ratio, and non-IgG immunoglobulin type each independently increase risk. Low-risk MGUS – small IgG band with normal free light chains – can be rechecked every two to three years, while high-risk patterns warrant annual review with a haematologist. No treatment is offered unless progression to a disorder causing organ damage is confirmed, because the risks of chemotherapy outweigh the benefit at the MGUS stage.

References

The clinical information on this page is drawn from peer-reviewed sources indexed by the US National Library of Medicine. Links go to the source so you can read it yourself.

Hypergammaglobulinemia (Polyclonal Gammopathy). In: StatPearls. Treasure Island (FL): StatPearls Publishing. NCBI Bookshelf NBK585137
Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564–569. PMID 11856795 · doi:10.1056/NEJMoa020494