The recent opportunity to treat populations with HER2-low disease using T-DXd, including patients treated with SOC (pre/post SG) in the context of TNBC, and the well-defined activity of T-DXd in current clinical practice, starting from the second line for HER2-positive mBC (also in patients receiving T-DM1 as prior/subsequent therapy), underscores the significance of this novel pharmacological class in the BC algorithm. The gene discussed is ERBB2; the disease is breast cancer.