Both HER-2 and EGFR are expressed in breast cancer and are implicated in its development and progression. The discovery of the association between HER-2 gene amplification and poor prognosis in breast cancer led to the development of HER-2 targeted therapies. Trastuzumab, a monoclonal antibody to HER-2, has significantly improved the prognosis for HER-2-positive breast cancer patients. It is now approved for the treatment of both HER-2-positive metastatic breast cancer and early stage HER-2-positive breast cancer. Recent results from trials of the dual HER-2 and EGFR tyrosine kinase inhibitor, lapatinib, also show very promising results in HER-2-positive breast cancer. A number of EGFR inhibitors have been tested in breast cancer clinical trials, but with limited effect. This may be due to difficulty in selecting the appropriate patient population, caused by the lack of definitive predictive markers for response to EGFR inhibition.