Identification of tumor genomic alterations predictive of therapeutic benefit from targeted therapy has improved clinical outcomes across a wide range of malignant neoplasms. Examples include EGFR-mutant non–small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors, ERBB2 (formerly HER2/neu)-amplified breast cancer treated with human epidermal growth factor receptor 2–specific antibodies, and tumors with microsatellite instability treated with immune checkpoint blockade. The gene discussed is ERBB2; the disease is neoplasm.