Multiple myeloma results from an interplay between the monoclonal malignant plasma cells and supporting nonmalignant cells in the bone marrow. Recent studies suggest that the final transforming event in this B cell disorder occurs at a late stage of B cell differentiation based on the characteristics of the immunoglobulin genes expressed by the malignant clone as well as surface markers present on the tumor cells. Recently, an increasing pathogenic role in this malignancy by the nonmalignant cells in the bone marrow has been suggested by several studies. Specific infection of these supporting cells by the recently identified Kaposi's sarcoma-associated herpes virus (KSHV) suggests a novel mechanism by which this nonmalignant population may lead to the development of this B cell malignancy and support its growth.