The issues considered in this Research Topic point to the need to better define the role of activating molecular alterations of HER2; refine HER2 clinical testing to design the most tailored treatment for breast cancer patients; and tailor anti-HER2 vaccines to prevent relapse in high-risk breast cancer patients or progression in patients with HER2-overexpressing minimal residual disease. This evidence concerns the gene ERBB2 and breast cancer.