To evaluate the mortality and causes of death in monoclonal gammopathy of undetermined significance (MGUS), we identified 1324 cases of MGUS in the period 1978-93 in North Jutland County, Denmark. Data on mortality were obtained by record linkage to the Danish Death Registry. There were 868 deaths in the MGUS cohort during 7785 years of follow-up vs. 409.6 expected, giving a standardized mortality ratio (SMR) of 2.1 (95% confidence interval 2.0-2.3). Malignant transformation was the cause of death in 97 patients vs. 4.9 expected, yielding a SMR of 20.0 (16.2-24.4), which explained about 20% of the excess mortality in the cohort. The mortality was increased for several other malignant and non-malignant causes of death during the first 4 years of follow-up. For late follow-up, 5-18 years after detection of the M-component, the overall SMR was 1.7 (1.5-1.9), and malignant transformation was the only cause of death with a substantial increase of SMR. Although malignant transformation is an important cause of death in MGUS patients, it did not entirely explain the increased mortality. MGUS patients often suffer from coexisting clinical conditions that increase the mortality, especially during the first years after detection of the M-component.