Germline mutations in BRCA1 and BRCA2 account for ~30 % of inherited breast cancer. RAD51C was reported as an additional breast/ovarian cancer susceptibility gene in some populations. There is a paucity of data on the putative contribution of this gene to inherited breast/ovarian cancer in Jewish high risk families. High risk Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1 or BRCA2, were screened for RAD51C germline mutations by direct sequencing of exons and flanking intronic sequences. Overall, 206 high risk women, 79 (38.3 %) of Ashkenazi origin, were genotyped for RAD51C mutations: 190 (92.3 %) with uni- or bilateral breast cancer (mean age at diagnosis 51.3 ± 11.1 years), 14 with ovarian cancer (mean age at diagnosis 55.6 ± 8.7 years), and two with both breast and ovarian cancer. No truncating mutations were noted, and two previously described missense mutations were detected: p.Ile144Thr and p.Thr287Ala in Iraqi and mixed ethnicity Balkan-North African participants, respectively. These missense mutations were evolutionarily conserved, possibly pathogenic, based on some prediction algorithms, and were not detected in any of healthy Iraqi (n = 60) and mixed ethnicity (n = 140), cancer free controls, respectively. Germline mutations in RAD51C contribute marginally to breast and ovarian cancer susceptibility in ethnically diverse, Jewish high risk families. The p.Thr287Ala missense mutation may be a recurring, pathogenic RAD51C mutation in ethnically diverse populations.