While amplification of the ERBB2 gene intrinsically defines the HER2+ class of BC and is a long-established predictive biomarker of response to HER2 targeting therapies such as trastuzumab and pertuzumab, the mutation status of the gene and its binding partner HER3/ERBB3 are now emerging as potential predictive biomarkers. The gene discussed is ERBB2; the disease is breast cancer.