Human herpes virus 8 (HHV-8) also known as Kaposi's sarcoma-associated herpes virus has been strongly implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. Recently, this gamma-herpes virus was also found in the nonmalignant bone marrow dendritic cells of the majority of myeloma patients. In addition, HHV-8 is also detectable in the peripheral blood of most myeloma patients. In contrast, this virus is rarely detected in close contacts of myeloma patients or healthy subjects. Furthermore, only about one-third of patients with monoclonal gammopathy of undetermined significance (MGUS) are infected with HHV-8. Sequencing of HHV-8 DNA isolated from myeloma patients shows both interpatient differences and conserved differences unique to myeloma compared to HHV-8 in other malignancies. Consistent expression of both the viral homologs of interferon regulatory factor and interleukin-8 receptor in myeloma suggests a possible role for these transforming viral genes in the pathogenesis of this disease.