Overexpression of the c-erbB-2 oncogene in sarcomas and small round-cell tumors of childhood. An immunohistochemical investigation. Amplification and overexpression of the c-erbB-2 oncogene have been associated with a poor prognosis in breast cancer. The present study evaluates c-erbB-2 protein over-production in sarcomas and in small round-cell tumors of childhood by applying an immunohistochemical technique to formalin-fixed, paraffin-embedded tissues. This technique had previously demonstrated high sensitivity for the detection of c-erbB-2 activation. One peripheral neuroepithelioma demonstrated equivocal immunoreactivity for c-erbB-2 protein. There was no evidence of c-erbB-2 protein overproduction in 11 angiosarcomas, 21 chondrosarcomas, 10 epithelioid sarcomas, 14 Ewing's sarcomas, 20 hepatoblastomas, nine leiomyosarcomas, 12 liposarcomas, 13 malignant fibrous histiocytomas, nine malignant lymphomas, 15 neuroblastomas/ganglioneuroblastomas, 16 neurofibrosarcomas, 10 osteosarcomas, seven peripheral neuroepitheliomas, 10 rhabdomyosarcomas, six synovial sarcomas, and 20 Wilm's tumors. We conclude that overproduction of the c-erbB-2 protein is rare or absent in these neoplasms and that its detection is therefore not likely to be of practical utility in their pathologic evaluation and prognostication.