Abstract ERG belongs to the ETS-family of transcription factors and is expressed in subsets of Ewing sarcomas, myeloid leukemias and prostate carcinomas due to chromosomal translocations. Normal expression of ERG has been detected in vascular endothelial cells. In this study we examined ERG-expression in selected adult and embryonic normal tissues, vascular tumors, and non-vascular tumors as controls. A mouse monoclonal antibody (CPDR ERG-MAb) that specifically recognizes ERG oncoprotein was developed at the Center for Prostate Disease Research. We have utilized CPDR ERG-MAb with a Leica automatic immunostainer in combination with the Leica's avidin-biotin free polymer-based detection system. Diaminobenzidine was used the chromogen. Tissues that demonstrated nuclear ERG-immunoreactivity were scored, and only nuclear immunoreactivity was counted as positive. Approximately 10% of examined tissues lacked any ERG-immunoreactivity suggesting that this epitope may be sensitive to sub-optimal preservation. In normal adult skin, tonsil, thymus, liver, kidney, pancreas and, stomach, and colon nuclear ERG-immunoreactivity was restricted to vascular endothelial cells. In human and mouse embryonic tissues wide-spread immonolocalization of ERG was observed in endothelial cells and restricted expression in precartillage, and hematopoietic tissues. Nuclear ERG-positivity was consistently observed in benign vascular tumors (n = 6, at minimum in each category): capillary and cavernous hemangiomas of different types, papillary endothelial hyperplasia, and lymphangioma. In spindle cell hemangioma, the endothelial component was positive and spindle cells negative. In malignant vascular tumors, majority of spindle cells and endothelial cells in Kaposi sarcomas (n = 11) and tumor cells in epithelioid hemangioendothelioma (n = 11) and angiosarcoma (n = 17), were positive. All non-vascular tumors (minimum 5 cases of each): glomus tumor, epithelioid sarcoma, synovial sarcoma, undifferentiated sarcoma, metastatic malignant melanoma, undifferentiated carcinomas of lung and small intestine, pulmonary adenocarcinomas, and malignant mesotheliomas were negative. Consistent with our previous report, In prostatic adenocarcinomas ERG oncoprotein was present in 45% of the examined cases, with no reactivity in non-neoplastic prostate. ERG oncoprotein is a promising marker for prostatic adenocarcinoma in sepration of it from no-neoplastic prostate and other adenocarcinomas. Our recent study revealed that detecting ERG may also be utilized for the diagnosis of angiosarcoma, epithelioid hemangioendothelioma, and endothelial components of hemangiomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 352. doi:10.1158/1538-7445.AM2011-352