Seven patients with plasma cell myeloma experienced an aggressive, terminal phase. This phase is characterized by rapidly enlarging soft-tissue masses with tumor morphologic characteristics similar to a poorly differentiated or large-cell (histiocytic) lymphoma, with rapid death, and often with fever, pancytopenia, decreasing levels of myeloma protein, and younger age. Median survival from the onset of the phase was four months. There was no response to single-agent or combination chemotherapy. In view of the extremely poor prognosis and lack of response to conventional treatment, patients experiencing this characteristic terminal phase should be considered candidates for innovative therapy.