Purpose: Prognostic biomarkers are needed to optimize treatment decisions for prostate cancer. Single nucleotide polymorphisms participate in the individual genetic background modulating risk and clinical outcomes of cancer. We tested whether EGFR polymorphisms are associated with prostate cancer clinical outcomes. Materials and Methods: The study population consisted of 212 patients with clinically localized prostate cancer treated with radical prostatectomy from 1997 to 1999. Resected prostatic tissues were genotyped with allele specific probes for 9 haplotype tagging single nucleotide polymorphisms, which were located in intronic, exonic and flanking regions of linkage disequilibrium in the EGFR gene. Correlations between alleles, and recurrence and survival data were investigated using univariate and multivariate genetic analysis models. Results: There was a statistically significant association between the single nucleotide polymorphism rs884419 and prostate cancer recurrence, as defined in the study by at least prostate specific antigen biochemical recurrence (log rank test p <0.001). The incidence of the recurrence risk enhancing genotype A/A was 3.1% vs 17.4% and 80% for the risk decreasing genotypes A/G G/G, respectively. Based on Cox proportional hazard regression modeling patients carrying G/G and A/G genotypes were associated with a decreased risk of prostate cancer recurrence compared to those with the A/A genotype (HR 0.10, 95% CI 0.02-0.41 and 0.13, 95% CI 0.04-0.46, respectively, p <0.002). Conclusions: These data suggest that a polymorphism flanking the EGFR gene is an independent prognostic genetic biomarker that predicts prostate cancer biochemical recurrence after radical prostatectomy.