Within the past 2 years, four separate groups have reported marked improvement in relapse-free survival when trastuzumab was added to adjuvant chemotherapy in patients with HER2-overexpressing breast cancer. These results add further credence to the relevance of this receptor as a tumor target. Despite the significant benefits observed in early and advanced HER2-positive breast cancer, overexpression of the receptor is still associated with a poorer prognosis and an increased risk of disease relapse, even in patients with primary operable disease. Besides cytotoxic chemotherapy, and possibly hormonal therapy, patients whose tumors exhibit resistance to trastuzumab have few molecular-targeted options available. Recently, lapatinib, a small molecule dual inhibitor of both HER2 and EGF receptors, has been developed to expand the options for treating HER-positive breast cancer.