Immunoglobulin M monoclonal gammopathy of undetermined significance (IgM-MUS) was diagnosed in 213 Mayo Clinic patients who were residents of 11 counties in southeastern Minnesota from 1960 to 1994. During long-term follow-up, 29 (14%) developed non-Hodgkin lymphoma (n = 17), Waldenström's macroglobulinemia (WM; n = 6), chronic lymphocytic leukemia (n = 3), and AL amyloidosis (n = 3) with relative risks of 15-, 262-, 6-, and 16-fold, respectively. The cumulative probability of progression to one of these disorders was 10% at 5 years, 18% at 10 years, and 24% at 15 years, approximately 1.5% per year. Smoldering WM was identified in 48 patients at Mayo Clinic from 1974 to 1995. During follow-up, 33 of the 48 patients progressed to symptomatic WM. The median time to progression was 4.6 years. The risk of progression to WM was 6% at 1 year, 39% at 3 years, and 55% at 5 years.