In addition, considering the high immunogenicity of HER2+ tumors and the preferable settings in which immunotherapy could be employed (presence of tumor, early lines in metastatic disease), HER2+ breast cancer may represent a fertile soil (i.e., availability of tumor tissue, fast clinical impact) also to test newer immunotherapies agents and to expand the knowledge of possible mechanisms to overcome immunotherapy resistance. The gene discussed is ERBB2; the disease is breast cancer.