In multiple myeloma, a bone marrow biopsy does three jobs: it confirms the diagnosis by counting abnormal plasma cells, it identifies genetic changes that predict how aggressive the disease will be, and it later shows how deeply treatment has worked. Blood and urine tests track the disease between biopsies, but the marrow sample is where the most important decisions are anchored.
This guide explains what the procedure involves, what the pathologist looks for, and when your team may repeat it during treatment.
What Is a Bone Marrow Biopsy?
A bone marrow examination removes a small sample of bone and bone marrow for laboratory study. It is used to diagnose many blood disorders, and it usually has two parts:
- Aspirate: a small amount of liquid marrow drawn up through a needle. It is used to look at individual cells under the microscope and for flow cytometry and genetic tests.
- Trephine (core) biopsy: a thin cylinder of bone with marrow inside. It shows the bone marrow architecture and how plasma cells are distributed.
Both samples are almost always taken from the back of the hip bone, the posterior iliac crest, in a single visit.
Why Myeloma Needs a Marrow Sample
Multiple myeloma is a cancer of plasma cells, the white blood cells that normally make antibodies. Myeloma plasma cells multiply in the marrow and usually release a single abnormal antibody, called the monoclonal protein (M-protein) or paraprotein.
Blood tests such as serum protein electrophoresis, immunofixation, and serum free light chains can detect the M-protein. However, the same protein can appear in milder, precursor conditions. Only the marrow shows how many clonal plasma cells are present, and that count is central to the diagnostic criteria.
How the Biopsy Confirms Diagnosis
Under the International Myeloma Working Group (IMWG) criteria, active myeloma requires clonal bone marrow plasma cells of 10% or more (or a biopsy-proven plasmacytoma), plus evidence of organ damage or a specific high-risk biomarker. The table below shows how the marrow result separates myeloma from related conditions.
| Condition | Clonal plasma cells in marrow | M-protein | Organ damage (CRAB) |
|---|---|---|---|
| MGUS | Less than 10% | Less than 3 g/dL | Absent |
| Smoldering myeloma | 10% to 59% | 3 g/dL or more (or marrow criterion met) | Absent |
| Active multiple myeloma | 10% or more | Usually present | Present, or a biomarker such as 60% or more marrow plasma cells |
CRAB stands for hyperCalcemia, Renal impairment, Anemia, and Bone lesions. A marrow plasma cell level of 60% or more counts as a myeloma-defining event on its own, even before organ damage appears. Imaging such as whole-body low-dose CT, MRI, or PET-CT is done alongside to look for bone lesions.
What the Laboratory Tests on the Sample
Several tests are run on a single marrow sample, each answering a different question:
- Morphology: a pathologist counts plasma cells and looks at their appearance.
- Immunohistochemistry: stains such as CD138 highlight plasma cells in the core, and kappa and lambda stains show whether they are clonal.
- Flow cytometry: distinguishes abnormal plasma cells from normal ones by their surface markers.
- FISH (fluorescence in situ hybridization): looks for chromosome changes on purified plasma cells.
FISH results shape risk assessment. Changes such as del(17p), t(4;14), and t(14;16) are regarded as high-risk features and are part of the Revised International Staging System (R-ISS), along with serum albumin, beta-2 microglobulin, and LDH. High-risk findings may lead your team to recommend more intensive or longer treatment.
Biopsy During and After Treatment
Once treatment starts, blood and urine M-protein levels are the main way to follow response. A repeat marrow biopsy is usually done at key moments:
- To confirm a complete response, which requires fewer than 5% plasma cells in the marrow along with disappearance of the M-protein on immunofixation.
- To measure minimal residual disease (MRD) using next-generation flow cytometry or sequencing, which can detect one myeloma cell among 100,000 normal cells or more.
- Before and after autologous stem cell transplant.
- When relapse is suspected, especially if blood markers are unclear, and to look for new genetic changes.
- In non-secretory myeloma, where no measurable M-protein exists and the marrow is the main way to judge disease.
MRD negativity is associated with longer remissions, and it is increasingly used to discuss treatment decisions, though how best to use it is still being studied.
Current treatment usually combines drug classes such as proteasome inhibitors (for example bortezomib), immunomodulatory drugs (lenalidomide), anti-CD38 antibodies (daratumumab), and corticosteroids, with autologous transplant for eligible patients. CAR T-cell therapy and bispecific antibodies are used in relapsed disease.
What to Expect During the Procedure
A bone marrow biopsy is an outpatient procedure that typically takes 20 to 30 minutes. You lie on your side or front, the skin over the hip is cleaned, and a local anesthetic numbs the skin and the bone surface. Some centers also offer light sedation.
Most people feel pressure during the core sample and a brief, sharp pulling sensation when the liquid marrow is drawn. Afterward the site may ache for a few days, and simple pain relief is usually enough. Serious complications such as significant bleeding or infection are uncommon.
One limitation is that myeloma can be patchy. A single sample may underestimate the disease if it misses a heavily involved area, which is why results are always read together with blood tests and imaging.
Key Takeaways
- The bone marrow biopsy is essential to diagnose multiple myeloma and tell it apart from MGUS and smoldering myeloma.
- FISH on marrow plasma cells identifies high-risk genetic changes that guide treatment intensity.
- Repeat biopsies confirm complete response and measure minimal residual disease.
- Blood and urine tests remain the main tools between biopsies.
- The procedure is brief and done under local anesthetic, with mild soreness afterward.
For more on how myeloma fits among other hematologic cancers, see our guide to hematological disorders and the bone marrow guide.
Frequently Asked Questions
Can multiple myeloma be diagnosed without a bone marrow biopsy?
In most cases, no. Blood tests may strongly suggest myeloma, but the marrow plasma cell count is part of the diagnostic criteria. The exception is when a biopsy of a single bone or soft-tissue tumor (a plasmacytoma) confirms the diagnosis, though a marrow sample is usually still taken to assess the extent of disease.
How often will I need a bone marrow biopsy?
There is no fixed schedule. Most patients have one at diagnosis and again at key points, such as confirming remission, assessing MRD, around transplant, or at relapse. Routine monitoring between these points relies on blood and urine tests.
Does a bone marrow biopsy hurt?
Local anesthetic numbs the skin and bone surface, so the main sensations are pressure and a brief pulling feeling during the aspirate. Soreness afterward usually lasts a few days and settles with simple pain relief.
What does MRD-negative mean in myeloma?
It means sensitive tests on the marrow found no detectable myeloma cells at a very low threshold, typically one in 100,000 cells or fewer. It is a strong sign of deep response, but it does not guarantee the disease will never return, so monitoring continues.
