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There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person‐years in the cohort by the geographically matched age, sex, and calendar year–specific cancer rates, and summing over all person‐years.The 9,547 patients from 23 centers were observed for a total of 76,948 patient‐years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05–1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13–3.49), and for non‐Hodgkin's lymphoma, it was 3.64 (95% CI 2.63–4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05–1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78).These results support the notion of an association between SLE and cancer and more precisely define the risk of non‐Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures. [ABSTRACT FROM AUTHOR]