An 8-year-old castrated male Paint Horse was referred because of generalized pruritus, alopecia, and intermittent fever. Results of gross evaluation of the skin and microscopic evaluation of skin scrapings were inconclusive. Histologic examination of skin biopsy specimens revealed vasculitis. The horse had persistent hypercalcemia; therefore, lymphosarcoma was considered a possibility. Ultrasonography revealed hypoechoic nodules within the parenchyma of the spleen and liver. Results of microscopic evaluation of an aspirate from a splenic nodule were suggestive of lymphosarcoma. The condition of the horse deteriorated, and it was subsequently euthanatized. Postmortem examination revealed diffuse lymphoma. In human beings, generalized pruritus may be an indication of serious internal disease, including malignancy. Paraneoplastic pruritus is most common in patients with Hodgkin's lymphoma but can also develop in patients with non-Hodgkin's lymphoma, leukemia, or a solid neoplasm. Lymphoma should be considered in the differential diagnoses when examining horses with generalized pruritus for which another cause cannot be identified.