AbstractA 36 year old homosexual, HIV positive, white male was evaluated for diffuse abdominal cramps. His work-up included a CT scan of the abdomen that revealed diffuse retroperitoneal adenopathy. A cervical lymph node biopsy showed follicular hyperplasia as has been described in HIV infection. An axillary lymph node biopsy disclosed tumor of uncertain origin by light microscopy. The differential diagnosis included large cell lymphoma, metastatic melanoma and metastatic germ cell tumor.Immunohistochemistry was initially misleading because of the false positive reactivity of HMB45 monoclonal antibody with tissue sections that had been fixed in B5 solution. Electron microscopic studies showed characteristic ultrastructural features of seminoma. Repeat immunohistochemistry with tissue fixed in formalin showed no reactivity with HMB-45 or S-100 and strong reactivity with placental alkaline phosphatase.Germ cell tumors are appearing in the literature as a“new set”of neoplasms which may have an increased incidence in males with HIV infection. This is the first case of seminoma in an HIV positive patient who presented with metastatic disease. (The J Histotechnol13:299, 1990)