The age-adjusted prevalence rate of monoclonal gammopathy of undetermined significance (MGUS) is three-fold higher in African Americans than whites. Similarly, there is a higher preponderance of multiple myeloma (MM) in African-American patients. Since the risk of progression of MGUS to MM is equal in both races, identification of exogenous and genetic risk factors of MGUS [such as genetic pre-disposition; diet; and chronic antigenic exposure related to sexually transmitted diseases, including human immunodeficiency virus (HIV) infection] is essential for unraveling the etiology of the racial disparity for MM. HIV infection, a well-documented risk factor for MGUS, is more frequent in African-American patients. Future epidemiologic studies dealing with plasma cell disorders should carefully examine the relationship between race, HIV infection status, prevalence of MGUS and its ultimate progression to MM.