Both the tumor cells and the microenvironment of dendritic stromal cells appear to be involved in the etiology of multiple myeloma. Switch translocations in myeloma tumor cells often involve oncogenes. These translocations have a clearly established role in the etiology of lymphoma and may prove to have a role in the transformation process of myeloma. Dendritic stromal cells infected with human herpesvirus-8 may provide a growth and antiapoptosis advantage for myeloma bone marrow stromal cells via viral interferon regulatory factor expression. In addition, increased vascular endothelial growth factor expression secondary to viral interleukin-8 receptor gene expression stimulates angiogenesis and inhibits development of uninfected dendritic cells, providing an advantage to infected dendritic cells. These recent advances in the understanding of the etiology of multiple myeloma provide potential new genetic, viral, and cytokine targets for therapy of this fatal malignancy.