Approximately 80% of invasive breast cancers are categorized as HER2-negative, as per ASCO–CAP guidelines [2,3,14]; however, across studies of patients with primary or metastatic breast cancer, an estimated 50–55% meet the criteria for HER2-low and 15–20% meet the criteria for HER2-ultralow breast cancer (Figure 1) [13,14,15,16,17]. The gene discussed is ERBB2; the disease is breast cancer.