We have analyzed 18 families with high incidence of breast cancer or breast and ovarian cancer for the presence of BRCA1 mutations. We identified 4 mutations in the BRCA1 gene in 4 unrelated probands who belong to families with at least 1 case of breast and 1 case of ovarian cancer. Two of the mutations reported in this study are novel (GAA(1172)-->TAA in family Naples 14, GAA(1765)-->TAA in family Naples 20) whereas the others are already present in the Breast Cancer Information Core Electronic Database (http://nchgr.nih.gov/ Intramural research/Lab transfer/Bic/) (5382insC in family Naples 18 and 2080delA in family Naples 19). Conversely, no mutation in the BRCA1 gene was detected in 14 families characterized by 2 or more cases of breast cancer only, even if bilateral and with early-onset. These results indicate that germline mutations in the BRCA1 gene highly predispose for a cancer syndrome that involves the presence of both breast and ovarian cancer.