The aims of this study were to evaluate and compare the HER2 gene amplification status in invasive and adjacent in situ breast carcinoma, using bright-field in situ hybridization, and to document the possible presence of HER2 genetic heterogeneity (HER2-GH) in both components. A cohort of 100 primary invasive carcinomas (IC) associated with carcinoma in situ (CIS) were evaluated for HER2 gene amplification by SISH according to the 2013 ASCO/CAP HER2 guideline.