A total of 42 cases undifferentiated large cell tumors were stained by immunoperoxidase techniques using antibodies against leukocyte common antigen (LCA) and epithelial membrane antigen (EMA). In 18 of the 21 cases studied, initially diagnosed as malignant lymphoma or Hodgkin's disease, reactivity with monoclonal anti-LCA (and noreactivity with monoclonal anti-EMA)indicated that the tumor was a lymphomas. The remaining 3 cases gave the reverse reaction pattern and therefore were classified as carcinoma. One out of 16 cases diagnosed as undifferentiated carcinoma proved to be a case of mialignant lymphoma in 5 patients in whom the original diagnosis was uncertain, a definite diagnosis was possible in all cases and 3 of these proved to be large cell lymphoma; the remainders, undifferentiated carcinoma. It is suggested that the staining of undifferentiated human neoplasms using combinations of antibodies reactive with epithelial and lymphoid cells may result in much greater diagnostic accuracy.