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Hemangiosarcoma is an uncommon tumor in horses. We characterized 3 cases of equine renal hemangiosarcoma, focusing on clinical and pathologic features, and describe occurrence of the epithelioid variant of hemangiosarcoma in one of these cases. Nuclear expression of phosphorylated STAT3 (pSTAT3) was assessed to analyze potential inappropriate STAT3 activation as a component of tumor pathogenesis. Clinical signs in the 3 horses included insidious weight loss, followed in one case by serosanguineous nasal discharge and terminal epistaxis, and nonspecific signs of abdominal pain. Two of the hemangiosarcomas had a classical histopathologic appearance; in the other, neoplastic cells were polygonal and were arranged in densely packed sheets, resembling the epithelioid variant. Cross-reactivity of a pSTAT3 antibody was established by demonstration of pSTAT3 expression in the epithelium of glabrous skin by immunoblotting and immunohistochemistry. In the epithelioid hemangiosarcoma, ~40% of neoplastic cells exhibited nuclear pSTAT3 expression, but in the other 2 cases, expression was weak and variable in the neoplastic population, although stromal cell pSTAT3 activity was evident in pulmonary metastases in one case. [ABSTRACT FROM AUTHOR]