Approximately 70% of early-stage breast cancers (EBC) are human epidermal growth factor 2 (HER2) negative.1 Importantly, the characterization of HER2 has dramatically evolved over the last 3 decades, from a poor prognostic biomarker to a predictor of clinical benefits of anti-HER2 therapy.2,3 Strikingly, patients who are defined as HER2-low based on the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP)4 guidelines can benefit from novel anti-HER2 antibody-conjugated (ADC) therapy. The gene discussed is ERBB2; the disease is breast cancer.