A rare case of diffuse large cell lymphoma (DLL) arising in the stomach of a patient with long-standing chronic lymphocytic leukemia (CLL) has been examined by a combination of immunophenotypic and gene probe methods. Both the resected lymphoma and the CLL (obtained from an infiltrate in perigastric lymph nodes) expressed surface membrane markers consistent with a B-cell origin (HLA-DR+; B1+; B4+), but surface membrane immunoglobulin (SmIg) could be detected only on the CLL cells (SmIgM lambda+). Neither neoplasm expressed cytoplasmic immunoglobulin. DNA probe analysis using the Southern blot method and probes to the joining (J-H) region of the immunoglobulin heavy chain gene and to the constant (C) regions of the immunoglobulin kappa and lambda light chain genes revealed different light and heavy chain gene rearrangements in the two neoplasms. These findings suggest that the large cell lymphoma arose from a different clone than the CLL and the development of large cell lymphoma may have represented a de novo neoplastic event in a predisposed person.