The objective of this study was to determine the relative risks of malignancy and of site-specific malignancies in patients with systemic lupus erythematosus (SLE). A cohort of 297 patients (91% Caucasian) with SLE were seen between 1975 and 1994 and followed for a mean of 12 years at the University of Saskatchewan Rheumatic Disease Unit. Expected cancer incidence rates were determined based on Province of Saskatchewan population statistics matched to each study patient for age, sex and calendar year of follow-up. Standardized incidence ratios (SIRs) of observed to expected cancers and 95% confidence intervals (95% CI) were calculated. A total of 27 cases of cancer were observed, whereas only 16.9 were expected (SIR 1.59 (95% CI 1.05-2.32)). For site-specific malignancies, an excess of cancer of the cervix (SIR 8.15 (95% CI 1.63-23.81)) as well as hemopoietic malignancy (SIR 4.9 (95% CI 1.57-11.43)) was found. The hemopoietic cancers were predominantly non-Hodgkin's lymphoma (SIR 7.01 (95% CI 1.88-17.96)). We did not find an association of malignancy with known risk factors, including use of cytotoxic agents. Increased risk of malignancy, notably non-Hodgkin's lymphoma and perhaps cervical cancer, should be regarded as a complication of SLE.