A 53-year-old male was diagnosed as having ataxic polyneuropathy associated with IgM-kappa monoclonal gammopathy in January 1988. Plasmapheresis and chemotherapy with chlorambucil and Melphalan-Prednisolone were effective for his neuropathy, but hemolytic anemia appeared in February 1989. The diagnosis of low-titer cold agglutinin disease (IgM-kappa) with anti-Pr2 specificity was made. Hemolytic anemia became refractory to high-dose corticosteroids, and fever, hepatosplenomegaly and severe pancytopenia appeared in January 1990. Bone marrow involvement of malignant lymphoma (mu, kappa) was found, and he died of pneumonia and gastrointestinal bleeding after the start of chemotherapy. Postmortem examination revealed a widespread infiltration of malignant lymphoma, diffuse, large cell (B-cell) type. Erythrophagocytic histiocytes also increased in bone marrow, liver, spleen and lymph nodes, as if there were hemophagocytic syndrome associated with lymphoma present. In addition to the high thermal amplitude of cold agglutinin in this case, the systemic activation of histiocytes induced by the development of malignant lymphoma may be responsible for progressive hemolysis and severe pancytopenia.