Waldenström's macroglobulinemia is a lymphoplasmacytic lymphoma. Genetic analysis has revealed a common mutation (L265P) in MYD88 in more than 90% of patients with this disease. The mutation appears to activate NF-κB. Waldenström's macroglobulinemia is an IgM-secreting lymphoplasmacytic lymphoma (LPL). 1 , 2 Clinical manifestations of Waldenström's macroglobulinemia include cytopenia resulting from bone marrow infiltration by lymphoplasmacytic cells, paraprotein-related cryoglobulinemia, the cold agglutinin syndrome, demyelinating neuropathy, and symptomatic hyperviscosity. 3 The oncogenic basis of Waldenström's macroglobulinemia has not been defined. Familial clustering of Waldenström's macroglobulinemia and other B-cell disorders suggests that genetic factors play a role in the pathogenesis of Waldenström's macroglobulinemia in certain patients. 4 – 6 IgM monoclonal gammopathy of unknown significance (MGUS) is characterized by the presence of a monoclonal IgM protein and the absence of bone marrow disease involvement on histologic examination. 1 IgM . . .