Although metastatic breast cancer patients with the discordance between IHC and HER2 copy numbers seemed to show a low probability of responding to HER2-targeted therapy [11], there has been no study to clarify that single-gene overexpressers with operable breast cancer will respond to trastuzumab, and the mechanisms for the possible resistance to the trastuzumab-containing chemotherapy. The gene discussed is ERBB2; the disease is breast cancer.