Approximately half of all prostate cancers harbor recurrent gene fusions involving ETS transcription factors. The most common gene rearrangement is the fusion of the 5' untranslated region of TMPRSS2 (an androgen-regulated gene) and ERG (a member of ETS transcription factor family). TMPRSS2:ERG fusion is cancer-specific and results in ERG protein overexpression. ERG fusion is associated with adverse clinicopathologic predictors, metastases, and disease-specific death in non-PSA screened populations. In a cohort of active surveillance patients, it is correlated with increased tumor volume and higher Gleason grade. The effect of ERG fusions on aggressive features or outcome following radical prostatectomy is less clear and needs further elucidation.