The transcription factor erythroblastosis virus E26 transforming sequence related gene (ERG) acts as a regulator of important cellular functions to promote endothelial homeostasis. ERG expression has been observed in both benign and malignant vascular endothelial tumors, such as hemangiomas and Kaposi’s sarcoma, respectively. Carcinomas of the breast, colon and urothelium have shown a lack of ERG expression, whereas the presence of the protein has been confirmed in a subset of prostate carcinoma cases. Anti-ERG may be a useful tool to identify vascular endothelial neoplasms and to distinguish prostate carcinomas from epithelial tumors of non-prostatic origin.