The aim of this study was to verify whether histopathological features of extratumoral and of primary tumor breast tissue could play a role in identifying patients with familial characteristics. We examined the clinicopathological features of 504 patients with sporadic or familial breast cancer stratified for risk of BRCA mutation. Patients with a higher risk of being carrier of BRCA gene mutations were significantly associated with tumor poor differentiation (p=0.003), positive lymph node invasion (p=0.02) and presence of vascular peritumoral invasion (p=0.008). Among the extra-tumoral lesions, only the epithelial proliferative lesions were related to higher mutation risk both in the overall series and familial patients (p<0.0001 and p=0.003, respectively). Interestingly, a significant difference in terms of high mutation risk was observed in usual ductal hyperplasia lesions (UDH), (p=0.002). We suggest that vascular peritumoral invasion and UDH lesions could predict a higher mutation risk of BRCA1 and BRCA2 genes and help in individuating patient candidates to further molecular analysis.