- Objective. To estimate the risk of cancer in patients with systemic lupus erythematosus (SLE). Methods. Patients with SLE (n = 724) have been followed prospectively, for 24 years, at the University of Toronto Lupus Clinic. The diagnosis of cancer was confirmed by histologic or autopsy reports. Standardized rates of cancer and standardized incidence rates (SIR) (ratio of observed-to-expected cancers) were used to estimate the risk for cancers. Results. Twenty-four cancers were identified in 23 SLE patients (3.2%) during 7,233 patient-years of followup. Compared with the Ontario population, the overall estimated risk for all cancers was not increased in the lupus cohort (SIR 1.08, 95% confidence interval 0.70–1.62). A 4.1-fold increased risk for hematologic cancers was observed, due mainly to an increased risk of non-Hodgkin's lymphoma. The risk for cancer was significantly lower in the SLE cohort compared with patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc). Conclusion. SLE is associated with a lower risk of all cancers compared with RA and SSc, but an increased risk for non-Hodgkin's lymphoma compared with the general population.