The aim of the study was to evaluate the performance of immunohistochemical MS110 expression in a series of familial and sporadic breast cancer patients. An immunohistochemical study was performed on TMA samples from 93 sporadic and 94 familial breast cancer patients with (7/94) and without BRCA1 germline mutations. BRCA1 protein expression level was evaluated using the monoclonal MS110 antibody. Immunohistochemistry, performed on TMA samples, showed positive nuclear staining for BRCA1 in 34 sporadic and 37 familial breast tumours, respectively. All the tumours from patients carrying BRCA1 mutations showed complete loss of both BRCA1 and ERalpha expression, regardless of the type of mutation. The percentage of MS110 positive cases was significantly lower in mutated versus wild type BRCA1 familial cases (p=0.02) while the percentage of patients with higher ERalpha expression was significantly lower in BRCA1-mutated versus BRCA1-wild type familial patients (p=0.05). Interestingly, the presence of the E1038G polymorphism in BRCA1 exon 11 was significantly associated with protein expression (p=0.029). The frequency of MS110 negative cases also detected in BRCA1-wild type tumours, points to the inability of the BRCA1 IHC expression in discriminating between familial and sporadic breast cancer.