The authors report a 60-year-old man with Richter's syndrome, or diffuse large cell lymphoma (DLCL) occurring in a patient with either chronic lymphocytic leukemia (CLL) or Waldenström's macroglobulinemia (WM). Surface marker analysis revealed that the WM showed mu kappa surface immunoglobulin (Ig) chains, and that the DLCL showed mu lambda Ig chains. Flow cytometric DNA analysis demonstrated DNA content differences between WM and DLCL, the former diploid and the latter aneuploid. The current study suggests that Richter's syndrome derives from two independent B-cell malignancies.