Forty-six cases of solitary plasmacytoma were reviewed for response to radiation and progression to multiple myeloma. Cases were classified as solitary plasmacytomas of bone (SPB) (32 cases) or extramedullary plasmacytomas (EP) (14 cases). There was an overall 93% response rate of the tumor to radiation therapy: 62% had a complete response after radiation therapy, whereas 31% had a partial response. Conversion to multiple myeloma was influenced by the type of plasmacytoma; 53% of the patients with SPB converting to myeloma versus 36% of the patients with EP. Time from diagnosis to conversion for patients with SPB showed no evidence of plateau, with conversion continuing to occur even after 17 years. The median survival time for patients after conversion to myeloma was 14.5 months and was not affected by time to conversion. Serum protein level, presence of monoclonal gammopathy, and size of primary lesion were of some prognostic significance in predicting conversion to myeloma. Adjuvant chemotherapy did not affect the incidence of conversion but did appear to delay conversion to myeloma. Seven patients in whom multiple sequential solitary plasmacytomas developed formed a distinct subset, with a median time to a second plasmacytoma of 63 months. In three of these patients, conversion to myeloma occurred subsequently. This study supports the idea of EP having a lower incidence of conversion to myeloma and a different natural history from SPB, with SPB likely to be multiple myeloma in evolution.