Previous studies suggested that appendectomy may affect cancer risk in the general population. No data on the effect of appendectomy on cancer risk in BRCA1 and BRCA2 carriers is available. Data on appendectomy, cancer type, and age at diagnosis were collected from BRCA1 (n = 677) and BRCA2 (n = 270) female Jewish Israeli mutation carriers counseled in a single medical center. Data were also collected on 225 consecutive ovarian cancer cases treated at the same medical center. Overall, 367/947 (38.7%) of mutation carriers had breast cancer (age at diagnosis 44.1 ± 10.4 years), 142 (15.0%) ovarian cancer (53.6 ± 10.1 years), and 438 (46.25%) were asymptomatic carriers (age at counseling 41.4 ± 11.2 years). Mean age at diagnosis of consecutive ovarian cancer cases was 53.6 ± 10.1 years. Of mutation carriers, 28/367 breast cancer cases (7.6%), 15/142 ovarian cancer cases (10.6%), and 11/438 asymptomatic carriers (2.5%) underwent prior appendectomy (P = 0.001 for breast/ovarian cancer when compared with asymptomatic carriers). In all but two cases, appendectomy was performed more than 10 years before cancer diagnosis or age at counseling. Of ovarian cancer patients, 12/225 (5.3%) underwent appendectomy, and in 10 appendectomy was performed 10 years or more before ovarian cancer diagnosis (P = 0.068 when compared with inherited ovarian cancer cases). This study suggests that prior appendectomy is more frequently noted in BRCA1 and BRCA2 carriers with breast and ovarian cancer than in unaffected mutation carriers. The mechanism for this association is elusive, and future analyses of ethnically diverse mutation carriers are needed to validate these results.