Avian v-ets erythroblastosis virus E26 oncogene homolog (ERG) is highly sensitive and specific for endothelial neoplasms and specific for prostate carcinoma. We characterized a rabbit anti-ERG antibody as an immunohistochemical agent to detect ERG expression in various tumors using tissue microarrays with a wide array of epithelial and mesenchymal tumors. ERG was positive in 63 (38%) of 168 prostate carcinomas and negative in all other epithelial tumors. ERG was positive in all 125 vascular lesions. It was also positive in the sarcomatoid component of a high-grade urothelial carcinoma and 6 (40%) of 15 meningiomas. Twelve (80%) of 15 meningiomas were positive for Fli1, including all 6 ERG-positive cases. Positive immunostaining with this antibody is therefore highly specific for prostate carcinoma and vascular lesions, with a few caveats. ERG is rarely detected in nonvascular mesenchymal tumors with this antibody. Furthermore, about 40% of meningiomas are also positive for ERG immunohistochemically, probably because of cross-reactivity with Fli1. © American Society for Clinical Pathology.