In prostate cancer, the ERG gene locus may undergo a chromosomal translocation with the androgen-regulated transmembrane protease serine 2 (TMPRSS2) gene, resulting in the expression of an TMPRSS2-ERG oncoprotein; a new diagnostic marker of prostate cancer. The TMPRSS2-ERG fusion has been found to be the most common proto-oncogene present in prostate cancers, occurring in about 50% of cases. Molecular methods (FISH, bDNA) have shown a strong correlation between TMRPSS2-ERG rearrangement status and ERG expression, as detected by IHC. ERG oncoprotein expression has been shown to be a highly specific marker for prostate cancer. Given the lack of ERG expression in a wide variety of normal epithelial tissues and tumors, and its robust presence in prostatic adenocarcinoma, detection of ERG by IHC is a valuable tool for diagnosing prostate cancer or determining prostatic origin. ERG is also high expressed in vascular endothelial cells, making it a very specific marker for vascular tumors.