Carcinosarcoma of the breast, often referred to as metaplastic carcinoma of the breast, is a rare malignancy with two distinct cell lines described as a breast carcinoma of ductal type with a sarcoma-like component. Clinically, carcinosarcoma of the breast is an aggressive breast cancer. The prognosis for carcinosarcoma of the breast is less favorable compared to more common types of breast cancer such as infiltrating ductal or lobular carcinoma. Currently, the evaluation of breast carcinoma includes hormone receptor analysis of the tumor tissue, with those positive for estrogen or progesterone responding better to both hormonal and chemotherapy.Trastuzumab (Herceptin(R)) is available as an adjunct treatment for tumors which over-express the HER2/neu gene. Typically, metaplastic carcinomas of the breast do not express the estrogen or progesterone receptors and do not over-express the HER2/neu oncogene. As a result of this "triple negative" phenotype, such tumors tend to be more aggressive and are unlikely to respond to targeted therapy with Herceptin. The epidermal growth factor receptor HER-1/EGFR protein is expressed in the majority of metaplastic carcinomas and thus may serve as a potential therapeutic target for EGFR inhibitors such as gefitinib and cetuximab. The two cases we describe exemplify the aggressive nature of carcinosarcoma of the breast and support the findings that this tumor type does not express the common receptors found in other breast carcinomas. These case reports also emphasize the need for investigating the role for blockade of the HER-1/EGFR receptor with targeted therapies when found to be over-expressed in the primary tumor.