Ten cases of gynecologic malignancies, including three endometrial, two ovarian and four cervical carcinomas, were studied for the expression of a 185 kDa protein (ErbB-2), coded by a proto-oncogene, c-erbB-2, in primary lesions as well as in metastatic lesions. Positive immunoreactivity was observed in all primary adenocarcinomas but not from squamous cell carcinomas. Many adenocarcinoma cells in distant metastatic sites or in tertiary lymph nodes were strongly stained for ErbB-2. These metastatic cells also showed an expression of proliferating cell nuclear antigen (PCNA). Detection of ErbB-2 mRNA by a reverse-transcription polymerase chain reaction showed that the transcription occurred exclusively in adenocarcinomas. To our knowledge, this is the first report demonstrating ErbB-2 expression in distant metastatic lesions of gynecologic cancers.