A 16-year-old Irish Hunter cross gelding was evaluated for a 3-month history of progressive weight loss, persistent pyrexia, potential thrombocytopenia and a year-long persistent cough. Significant initial physical examination and laboratory findings included a body condition score of 2/9, mild unilateral epistaxis and mucoid nasal discharge, edematous hind limbs, a preputial mass, and clinical pathologic test results indicative of a protein-losing enteropathy and systemic inflammation. Tracheoscopy and tracheal wash cytologic examination and aerobic bacterial culture revealed ecchymotic hemorrhage on the tracheal mucosa and septic, suppurative inflammation due to Streptococcus equi ssp zooepidemicus, respectively. Cytologic examination of a fine needle aspirate from a splenic nodule (identified on ultrasonographic examination) contained numerous neoplastic lymphocytes with red cytoplasmic granules. A diagnosis of lymphoma of granular lymphocytes was made and the horse was euthanized. Bone marrow aspirate cytologic examination, gross and histopathologic necropsy findings, and immunohistochemical staining of formalin-fixed necropsy tissues supported a diagnosis of lymphoma of presumptive cytotoxic T cell and intestinal origin, with metastasis to the spleen, mesenteric lymph nodes, bone marrow, trachea, and prepuce.