Background. Mutations in the BRCA1 and BRCA2 genes are associated with increased risk of breast, ovarian, and several other cancers. The purpose of the present study was to evaluate the incidence of cancer in first-and second-degree relatives of BRCA mutation carriers compared with the general population. Materials and Methods. A total of 1,086 pedigrees of BRCA mutation carriers was obtained from a prospectively maintained, internal review board-approved study of persons referred for clinical genetic counseling at the University of Texas MD Anderson Cancer Center. We identified 9,032 firstand second-degree relatives from 784 pedigrees that had demonstrated a clear indication of parental origin of mutation. Standardized incidence ratios (SIRs) were used to compare the observed incidence of 20 primary cancer sites to the expected incidence of each cancer based on the calculated riskestimates according to each subject's age, sex, and ethnicity.