Multisystemic, eosinophilic, epitheliotropic disease and intestinal lymphosarcoma were diagnosed in a Paso Fino mare that presented with anorexia and weight loss. The stomach, ileum, cecum, colon, pancreas, and lungs were infiltrated by large numbers of eosinophils forming prominent eosinophilic granulomas, as well as lymphocytes and plasma cells. Two jejunal masses composed of solid sheets of neoplastic lymphocytes were present. In contrast to the regions of inflammation, the infiltrates in these masses did not contain plasma cells, eosinophils, and eosinophilic granulomas. Immunohistochemically, the neoplastic lymphocytes expressed CD3 but not CD20 or kappa and lambda light chains, supporting a diagnosis of T-cell lymphosarcoma. Concurrent diagnoses of hypereosinophilic syndrome and lymphosarcoma in this horse and several humans suggest that the multisystemic eosinophilic and lymphoplasmacytic infiltrates were caused by the clonal proliferation of T-lymphocytes that secreted interleukin-5 triggering differentiation and activation of eosinophils.