In patients with early-stage estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative breast cancer, clinicians should consider using multigene profiling assays (i.e., Oncotype DX, MammaPrint, Prosigna, EndoPredict, and Breast Cancer Index) to help guide the use of systemic therapy. The gene discussed is ERBB2; the disease is breast cancer.