Clinical, laboratory and tissue findings from 37 horses with lymphoma were investigated. Horses ranged in age from 0.3 to 20.5 years (median 5.0 years) and included 18 females and 19 males. Weight loss (n = 25) and ventral edema (n = 21) were the most common historical and physical abnormalities. The most common laboratory abnormalities were hyperfibrinogenemia (n = 26), hypoalbuminemia (n = 19), anemia (n = 19), leukemia (n = 14), hyperglobulinemia (n = 13), and thrombocytopenia (n = 13). Thirty-four tumors involved multiple lymphoid tissues and abdominal or thoracic organs, and 3 tumors were restricted to cutaneous and subcutaneous sites. Histopathologically, all tumors diffusely effaced normal lymph node architecture. Tumor cell morphology was heterogeneous in 17 tumors, and 8 tumors had marked histiocytic and multinucleated giant cell infiltrates. Extensive necrosis or focal fibrosis was present in 22 and 4 lymphomas, respectively. Staining of tumor sections with antibodies against CD3 and CD79alpha molecules resulted in classification of T-cell (n = 26) or B-cell (n = 7) origin. Four tumors could not be classified. Most T-cell tumors comprised small to medium CD3(+) lymphocytes, whereas 5 of 7 B-cell tumors were infiltrated by numerous small T lymphocytes and classified as T-cell-rich B-cell lymphoma. Neither estrogen nor progesterone receptor expression was consistently identified by immunochemical assessment of tumor tissues. Fresh tumor cells from 6 horses bound antibodies reactive with equine CD4, CD5, CD8, CD21, or major histocompatibility class II molecules, confirming T-cell (n = 5) or B-cell origin (n = 1). These findings suggest that T-cell lymphoma is more common than B-cell lymphoma in horses and that inflammation, possibly from tumor cytokine production, is frequent.