The introduction of trastuzumab and more recently of other anti HER2 treatments such as pertuzumab, and trastuzumab-emtansine (T-DM1) in early-stage and advanced HER2 positive breast cancer (BC) patients, has completely changed the natural history of the tumor both in terms of time to recurrence and survival [1–6]. The gene discussed is ERBB2; the disease is breast cancer.