African American (AA) men have a higher incidence and significantly higher mortality rates from prostate cancer than white men, but the biological basis for these differences are poorly understood. Few studies have been carried out to determine whether there are areas of allelic loss or gain in prostate cancers from AA men that are overrepresented in or specific to this group. To better understand the molecular mechanisms of prostate cancer in AA men, we have analyzed 20 prostate cancers from AA men with high-density single-nucleotide polymorphism arrays to detect genomic copy number alterations. We identified 17 regions showing significant loss and 4 regions with significant gains. Most of these regions had been linked to prostate cancer by previous studies of copy number alterations of predominantly white patients.We identified a novel region of loss at 4p16.3, which has been shown to be lost in breast, colon, and bladder cancers. Comparison of our primary tumors with tumors from white patients from a previously published cohort with similar pathological characteristics showed higher frequency of loss of at numerous loci including 6q13-22, 8p21, 13q13-14, and 16q11-24 and gains of 7p21 and 8q24, all of which had higher frequencies in metastatic lesions in this previously published cohort. Thus, the clinically localized cancers from AA men more closely resembled metastatic cancers from white men. This difference may in part explain the more aggressive clinical behavior of prostate cancer in AA men.