Phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) mutations are commonly found in prostate cancer. Although mouse studies have demonstrated that PTEN and ERG cooperatively interact during tumorigenesis, human studies examining these genes have been inconclusive. A systematic PubMed search including original articles assessing the pathogenesis of PTEN and ERG in prostate cancer was performed. Studies examining ERG's prognostic significance have conflicting results. Studies examining PTEN and ERG simultaneously found these genes are likely to occur together, but cooperative tumorigenesis functions have not been conclusively established. PTEN mutations are associated with a range of prognostic features. However, the practical clinical utility of this information remains to be determined.