Alimentary neoplasia is rare in the horse, with the exception of lipoma. This paper describes a case of a large colon lymphoma in a mare in which metastasis to the liver caused encephalopathy and severe neurologic signs. Differential diagnoses for encephalopathy in the adult horse including causes of advanced liver disease and gastrointestinal disturbances are discussed. In addition, the pathophysiology of liver disease leading to encephalopathy is reviewed.