The term "aggressive phase" has been applied in multiple myeloma to the development of rapidly enlarging extramedullary soft tissue masses or of bone marrow transformation with histologic features resembling high-grade or anaplastic lymphomas. One hundred and one patients who fulfilled this definition were identified in a review of the literature. Eighty-six patients had soft tissue or visceral involvement and 15 bone marrow involvement. The mean age at initial diagnosis of myeloma was 53 years, suggesting that the aggressive phase may be more likely to develop in younger patients. A disproportionate percentage of these patients have an IgA gammopathy. Following the onset of the aggressive phase, these patients have a rapidly fatal course, refractory to therapy, with a mean survival of less than 3.5 months. It is hypothesized that this aggressive phase represents part of the natural history of multiple myeloma, analogous to the terminal transformations associated with other relatively indolent myeloproliferative and lymphoproliferative disorders. Studies are reviewed supporting the proposition that the clinical and morphological changes associated with the aggressive phase result from a clonal evolution of the original malignant cell line and do not represent the development of an independent new neoplasm.