Multiple myeloma (MM) is a hematologic cancer with a prominent racial disparity between African Americans and European Americans. African Americans are two-to-three times more likely to be diagnosed, but they have a better prognosis. Cytogenetic abnormalities are associated with prognosis and clinical presentations, which can provide insight into disease outcome, too. This study aimed to assess the basis of racial disparities observed in prevalence and prognosis by comparing racial differences in cytogenetic abnormalities and clinical presentations in MM patients. Conventional FISH and MACS FISH, a more sensitive assay in detection of cytogenetic abnormalities, were compared first. MACS FISH was able to detect a higher frequency of all cytogenetic abnormalities. The comparison of cytogenetic abnormalities and clinical presentations between the two races from MACS FISH supported the view that European Americans have a poorer prognosis than African Americans possibly to a higher frequency of high-risk cytogenetic abnormalities associated with more severe clinical presentations in European Americans.