Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android


  • Monoclonal immunoglobulin (ie, paraprotein) in the serum (< 3 g/dL [< 30 g/L]) or urine.

  • Clonal plasma cells in the bone marrow < 10% (if performed).

  • No symptoms and no organ damage from the paraprotein.


MGUS is present in 1% of all adults (3% of those over age 50 years and more than 5% of those over age 70 years). Among all patients with paraproteins, MGUS is far more common than plasma cell myeloma. MGUS is defined as bone marrow clonal plasma cells less than 10% in the setting of a paraprotein in the serum or urine (serum M-protein less than 3 g/dL [30 g/L]) and the absence of plasma cell–related end-organ damage. If an excess of serum free light chains (kappa or lambda) is established, the kappa to lambda ratio is 100 or less or 0.01 or greater (otherwise, this is diagnostic of plasma cell myeloma). In approximately one-quarter of cases, MGUS progresses to overt malignant disease in a median of one decade. The transformation of MGUS to plasma cell myeloma is approximately 1% per year. Two adverse risk factors for progression of MGUS to a plasma cell or lymphoid malignancy are an abnormal serum kappa to lambda free light chain ratio and a serum monoclonal protein (M-protein) level 1.5 g/dL or greater. Patients with MGUS have shortened survival (median 8.1 years vs 12.4 years for age- and sex-matched controls). In addition, 12% of patients with MGUS will convert to primary amyloidosis in a median of 9 years. Plasma cell myeloma, smoldering plasma cell myeloma, and MGUS must be distinguished from reactive (benign) polyclonal hypergammaglobulinemia (common in cirrhosis or chronic inflammation).


To establish the diagnosis, serum and urine should be sent for PEP and IFE to search for a monoclonal protein; serum should be sent for free light chain analysis and quantitative immunoglobulins. Additional tests include a hemoglobin and serum albumin, calcium, and creatinine. If these additional tests are normal (or if abnormal but otherwise explained), then a bone marrow biopsy is usually deferred provided the serum M-protein is less than 3 g/dL (less than 30 g/L). In asymptomatic individuals, a skeletal survey (radiographs) is performed, but if there are some bone complaints or a question regarding bone disease, MRI or PET/CT imaging is preferred. MGUS is diagnosed if patients do not meet the criteria for smoldering plasma cell myeloma or plasma cell myeloma.


Patients with MGUS are observed without treatment.

Atkin  C  et al. What is the significance of monoclonal gammopathy of undetermined significance? Clin Med (Lond). 2018;18:391.
[PubMed: 30287433]  
Kyle  RA  et al. Long-term follow up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018;378:241.
[PubMed: 29342381]  
Seth  S  et al. Monoclonal gammopathy of undetermined significance: ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.