Overexpression of the HER2/Neu (ErbB2) proto-oncogene is associated with breast cancer progression and poor patient prognosis. Herceptin (trastuzumab) is a humanized IgG1 against the ectodomain of the HER2 receptor. In combination with chemotherapy, it induces regression of HER2-overexpressing metastatic breast tumors and prolongs patient survival. Single-agent Herceptin in patients with HER2-amplified breast tumors also induces a definite objective response and clinical benefit rates, and is well tolerated. These data suggest that Herceptin is an effective first-line single-agent therapy for a predictable cohort of metastatic breast cancers and can therefore be used as a platform for therapeutic discovery against tumors that overexpress HER2.