In cancer cells, the ErbB2 receptor tyrosine kinase can be activated in two ways: by overexpression or by ligand-mediated stimulation of another ErbB receptor. The ErbB2-targeting antibody trastuzumab (Herceptin) is used for treatment of metastatic breast cancer patients whose tumors overexpress ErbB2. A new structural study in this issue of Cancer Cell reveals how targeting ErbB2 with another antibody, pertuzumab (Omnitarg), prevents ligand-induced dimerization of ErbB2 with the other ErbB receptors. Pertuzumab's novel mode of action might offer additional therapeutic opportunities for treatment of tumors expressing ligand-activated ErbB2.