2C4 (Pertuzumab, Omnitarg) is a monoclonal antibody targeting p185 her2/neu, which is overexpressed in 30% of invasive breast cancer. 2C4 is currently in phase II clinical trials for several types of cancers. This antibody has been reported to disrupt the association between p185 her2/neu and ErbB3. In our studies of epidermal growth factor receptor (EGFR)–p185 her2/neu heterodimerization, we noted that 2C4 formed associations with the EGFR–p185 her2/neu receptor complex. Our data argue against 2C4 as a universal heterodimerization blocker for p185 her2/neu, but indicate that cocktails of monoclonal antibodies binding distinct interaction surfaces of p185 her2/neu will emerge as the most potent targeted therapy.