The purpose of this study was to determine if there is an increased risk of acute leukemia and myelodysplastic syndromes (MDS) in persons with monoclonal gammopathy of undetermined significance (MGUS). We used a large population-based cohort of individuals systematically screened for the presence or absence of MGUS. MGUS status was then linked to the diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and MDS. A total of 17 315 patients age 50 and older (605 MGUS and 16 710 controls) with a cumulative 435 021 person-years of follow-up were studied. MGUS patients had a significantly higher risk of developing MDS compared with controls, hazard ratio 2.4 (95% CI 1.08, 5.32), P=0.031. There was no statistically significant increase in the risk of AML (RR 1.36 P=0.675), and no increased risk of developing ALL.