Regarding the post-analytical phase, the lack of consistent epithelial internal positive control for HER2 within non-neoplastic breast tissue, HER2 intratumoral heterogeneity, particularly in HER2-low breast cancer, and the semi-quantitative and subjective mode of HER2 assessment may lead to inter-observer variability affecting the accuracy of the results[44,48,49]. This evidence concerns the gene ERBB2 and breast cancer.