ERG expression has been proposed to signify molecular subtype of PCA. However, its significance in early onset prostate cancer (PCA) is not characterized. Materials and methods ERG protein expression was investigated in a cohort of 121 men diagnosed with localized PCA at\50 years of age with a mean follow-up time of 65.7 months. ERG was correlated to patients’ outcome and clinical-pathological parameters using univariate and multivariate analysis. Results ERG expression was detected in 76/118 (64.4 %) analyzable patients’ samples and showed interfocal heterogeneity (differences between foci) in 17/118 (14.4 %) patients. There was significant association between ERG expression and Gleason score (p = 0.022), but not with any other clinical-pathologic parameter, including presurgical PSA levels, tumor volume, pathological stage, surgical margin or lymph-vascular invasion. ERG had significant effect on the rate of biochemical relapse following radical prostatectomy, with ERG positive patients showing higher relapse rates vs. ERG negative patients (p = 0.007). However, considering time till biochemical relapse post-radical prostatectomy, ERG expression showed positive insignificant trends (p = 0.071). Notably, and of great significance, in this cohort of early onset disease, none of the ERG negative PCA patients exhibited biochemical relapse. Conclusion The study results suggest that ERG expression may be of added prognostic value in localized prostate cancer in patients with early onset PCA. However, the issue of ERG interfocal heterogeneity observed may require the evaluation of several tumor foci to assess ERG status per case. Incorporating ERG status into existing nomograms may be of added prognostic value in patients with early onset PCA.