The configurations of immunoglobulin genes and T-cell receptor beta chain genes were analyzed by Southern blotting in DNA derived from nonlymphoid malignant tumors and lymphomas. Gene rearrangements were not detected in any of the 35 cases of nonlymphoid malignant tumors. On the contrary, they were shown in all 14 cases of non-Hodgkin's lymphomas, 2 of 3 cases of Hodgkin's disease and 2 cases diagnosed as non-Hodgkin's lymphoma or angioimmunoblastic lymphadenopathy. The differentiation by light microscopy between lymphoma and nonlymphoid malignant tumors was a diagnostic problem in five cases; the molecular genetic analysis of DNA was contributory in all five diagnostically difficult aspirates. By gene rearrangement studies, the diagnosis of lymphoma was confirmed in two cases and nonlymphoid malignant tumors were accurately indicated in aspirates diagnosed finally as rhabdomyosarcoma (one case) and carcinoma (two cases).