A 4-year-old Oldenburg mare was evaluated because of signs of lower airway disease and subsequently developed bilateral pleural effusion. Neoplastic cells were not identified in the fluid sample obtained via the initial thoracocentesis. A thoracic mass was detected radiographically, but its location prevented collection of a tissue sample. A diagnosis of lymphoma was made on the basis of results of immunophenotyping of pleural fluid specimens. Treatment of thoracic lymphoma in horses has been attempted, but there are limited data regarding chemotherapeutic-induced remission. In this horse, remission was achieved by use of a chemotherapeutic protocol consisting of administration of cytarabine, cyclophosphamide, and prednisolone. No adverse drug reactions were encountered during treatment. Immunophenotyping of cells in specimens of pleural fluid could be used to determine lymphocyte lineage and may be a useful alternative diagnostic modality when morphologic and cytologic examination of tissue specimens obtained via invasive techniques is not feasible.