Background: Numerous studies have reported a significantly higher incidence of PCa and/or adverse pathological features associated with African-American men compared to European-American men. Less however is known about the genomic disparities that exist between these two groups. In this report we compared the race-specific expression of biomarkers linked to PCa pathogenesis in a matched cohort of AA and EA men. Methods: PCa data from AA and EA patients were analyzed from four medical centers. Cases were matched based on CAPRA-S within each institution for a total sample size of 300 (121-AA; 179-EA). The distribution of mRNA expression levels of 20 validated biomarkers associated with PCa initiation and progression was compared by race using a false-discovery-rate adjusted Mann-Whitney U, and logistic regression models. Conditional logistic regression models were used to evaluate the interaction between race and biomarker expression for predicting pathologic T3 PCa. Results: Of 20 biomarkers interrogated, 6 showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include TMPRSS2-ERG (p<0.001), AMACR (p<0.001), SPINK1 (p=0.005), AR (p=0.018), SRD5A2 (p=0.005), and GSTP1 (p=0.021). Dysregulation of MYCBP (p=0.043) increases risk of pT3 disease in AA but decreases the risk in EA men, while the reverse is true for AMACR (p=0.013), TMPRSS2-ERG (p=0.026), FOXP1 (p=0.016), and GSTP1 (p=0.032). Loss-of-function mutation for tumor suppressors PTEN (p=0.046), TP53 (p=0.042), and RB1 (p=0.027), and dysregulation of AR (p=0.015), EZH2 (p=0.043), NKX3-1 (p=0.024), SRD5A2 (p=0.032), and SPOP (p=0.032) increased risk of pT3 disease for both AA and EA men. Conclusions: We have identified a subset of PCa biomarkers that predict risk of clinico-pathologic outcomes in a race-dependent manner. These biomarkers may in part explain the biological contribution to racial disparity in PCa outcomes between EA and AA men.