A 6-year-old thoroughbred gelding was presented with a history of blepharospasm and opacity in the OS of 1 weeks' duration. Ophthalmic examination findings were consistent with acute uveitis in the OS, and traditional treatment was initiated with systemic antibiotics and anti-inflammatory drugs, topical mydriatics, and corticosteroids. During the total treatment period of 4 weeks response to treatment was weak and the horse developed further problems such as cellulitis of the right hind limb with fever and eventually weight loss and dependent edema. Blood work was indicative of liver disease. Abdominal sonography revealed severe splenomegaly and slight hepatomegaly, and a liver biopsy confirmed malignant T-cell lymphoma. The horse was euthanized due to deteriorating general condition and subsequently underwent postmortem examination. Necropsy and histologic examination revealed a multicentric lymphoma with involvement of spleen, mesenteric lymph nodes, and OU. The findings in this case demonstrate that the differential diagnosis of intraocular and systemic lymphoma should be considered in any horse presenting with anterior uveitis, especially when uveitis is unresponsive to treatment and when additional systemic signs of illness such as lethargy, fever, weight loss, or dependent edema arise. Cytological examination of aqueous humor may provide a rapid diagnosis of intraocular lymphoma in eyes with clinical uveitis.