Paraffin-embedded sections of bone marrow from 131 patients were studied. The specificity of the immunoperoxidase technique for detecting intracellular kappa and lambda light chains of immunoglobulin was first evaluated in 34 cases of typical multiple myeloma or macroglobulinemia. The monoclonal light chain detected in the bone marrow myeloma was identical to the result of immunoelectrophoresis of serum or urine. By use of the same method, 97 cases in which the diagnosis was difficult were examined; cases included those of bone marrow plasmacytosis, lymphocytosis, and morphologically unusual cells. All marrow cells with monoclonal immunoglobulin detected by immunoperoxidase stain eventually proved to be a B-cell neoplastic or potentially neoplastic process. This study confirms the specificity of the immunoperoxidase stain and demonstrates its value in solving clinical diagnostic problems, that is, the diagnosis of nonsecretory myeloma and unusual morphology, differentiating the monoclonal plasmaproliferative disorders from reactive plasmacytosis or lymphoma from lymphocytosis.