Recent clinical trials using the HER2-directed antibody–drug conjugate T-DXd have already included patients exhibiting either IHC 1 + or 2 + /HER2 non-amplified in their HER2-low group (e.g., DB02 [NCT03523585]) or very low (“ultra-low”) HER2-expressing cohorts (HER2 IHC 0 < 1 + , weak staining in less than 10% of tumor cells, e.g., DB06 [NCT04494425]) eligible for therapy. This evidence concerns the gene ERBB2 and neoplasm.