To ensure targeted treatment, it would be useful to know at the time of diagnosis whether a BRCA mutation is causally related to an individual breast cancer. The aim of this study was to investigate in an unselected series of breast cancer patients the value of incorporating morphological and immunohistochemical features for the selection of patients who may benefit from BRCA1 genetic testing. In a retrospective approach, histopathological results of tumors from 897 women were reevaluated regarding age at diagnosis, subtype of cancer, tumor grade, and estrogen (ER), progesterone (PR), and Her2/neu receptor status, as well as p53 and Ki67 status. In all, 142 tumors fulfilled morphological criteria indicative of a BRCA1 mutation. Of the 59 women willing to participate, 26 women concomitantly showed a positive family history. Pathogenic BRCA1 germline mutations were detected in 7 of 18 women (39%) (95% confidence interval = 0.17-0.64). All BRCA1-associated tumors were of high grade, invasive-ductal subtype, and PR and Her2/neu negative, and 91% of the tumors were negative for ER; 60% of the tumors showed a high expression of p53 and 60% a high expression of Ki67. There was a significant difference with respect to grading (P = 0.001 for G3), ER negativity (P = 0.0075), Ki67 > or = 65% (P = 0.0039), and triple negativity (i.e., ER(-), PR(-), Her2/neu(-)) (P = 0.0019) between tumors of mutation carriers and noncarriers.