HER-2/neu is an oncogene located on chromosome 17, encoding a type 1 tyrosine kinase growth factor receptor. HER-2/neu is overexpressed in 25-30% of breast cancers, increasing the aggressiveness of the tumor. We describe HER-2/neu overexpression and her-2/neu oncogene amplification in a case of uterine carcinosarcoma occurring in a 46-year-old women who had undergone mastectomy and a 2-year postoperative treatment with tamoxifen for invasive breast cancer. This is the first study demonstrating HER-2/neu expression and her-2/neu oncogene amplification in a uterine carcinosarcoma that has developed in a patient given tamoxifen therapy. It still needs to be clarified whether HER-2/neu overexpression increases the aggressiveness of carcinosarcoma, or whether HER-2/neu has a direct role in its pathogenesis, as described in breast cancers. Our observation of the her-2/neu oncogene amplification does not shed light on the prognostic impact of uterine carcinosarcoma following tamoxifen therapy, but it may indicate the need for further studies of HER-2/neu overexpression in a larger series of uterine carcinosarcoma patients, and it may permit us to hypothesize about a therapeutic concept, including the inhibition of HER-2/neu by humanized monoclonal antibodies also in uterine carcinosarcoma patients.