BACKGROUND Waldenström macroglobulinemia (WM) and chronic lymphocytic leukemia (CLL) are related B-cell cancers that share several clinical and biological features. Both WM and CLL have associated precursor conditions: monoclonal gammopathy of undetermined significance (MGUS) of immunoglobulin M (IgM) type and monoclonal B-cell lymphocytosis (MBL), respectively. Recently, a case of MBL with an IgM MGUS was reported, suggesting a close biological relationship between these entities. While much is known about MGUS overall, investigations of IgM MGUS specifically have been fragmentary. METHODS In this article, we review data on the prevalence, clinical aspects and natural history of IgM MGUS, and focus on identifying gaps in our understanding of the complex relationships among B-cell malignancies and their precursors. RESULTS There appears to be marked heterogeneity in the prevalence of IgM MGUS across populations. However, studies have varied in definition, design, laboratory methods, and endpoints. IgM MGUS differs from non-IgM MGUS in certain respects, including prevalence across racial groups, rate of progression, and pattern of malignant outcomes. There are limited data regarding the coincident occurrence of IgM MGUS and MBL. CONCLUSIONS Future studies incorporating both protein electrophoresis and flow cytometry are needed to define the underlying spectrum and causes of precursor development, risk factors for progression, and markers that distinguish low- and high-risk precursor patients.