The recent approval of T-DXd in January 2025 for unresectable or metastatic HR-positive, HER2-low (IHC 1 + or IHC 2 +/ISH −) or HER2-ultralow (IHC 0 with membrane staining) breast cancer underscores the growing clinical relevance of low-level HER2 expression as a biomarker beyond traditionally defined HER2-positive (IHC 3 + or ISH +) cancers. The gene discussed is ERBB2; the disease is breast cancer.