Although in common clinical practice the treatment-decision process in terms of access to anti-HER2 targeted agents is driven by the dichotomization in HER2-positive (as defined by HER2 protein overexpression on IHC analysis—score 3+ and/or HER2 gene amplification on ISH assay) vs negative–which has been strengthened by 2018 ASCO/CAP guidelines9—HER2-negative breast cancer is characterized by a wide spectrum of HER2 expression levels10. This evidence concerns the gene ERBB2 and breast cancer.