High HER2 expression, as determined by IHC score or FISH analysis, cannot be considered per se a good indicator of HER2 addiction or the response to trastuzumab or other anti‐HER2 treatments because of (a) poor performance of IHC and FISH methods currently used to define HER2‐positive BC, which do not take into account HER2 protein levels or provide suboptimal quantification of HER2 levels, and (b) molecular heterogeneity of HER2‐positive neoplasms, with some tumors relying on other growth–proliferation pathways either independent or downstream of HER2 signaling. The gene discussed is ERBB2; the disease is breast cancer.