A 5-year-old cow was evaluated because of a 2-week history of ataxia and other vague neurologic signs. Previous treatments included intravenous and orally administered calcium, but improvement was not seen. Bilateral mucoserous nasal discharge and a pair of firm, smooth masses caudodorsal to the eyes were found on the frontal bones on physical examination. The cow's condition deteriorated rapidly within 48 hours; head pressing and inability to rise were observed. The frontal sinuses were radiographically normal. Trephination of the frontal sinuses revealed a space-occupying mass that was interpreted on histologic examination to be lymphosarcoma. Other evidence of neoplasia was not discovered on gross necropsy or histologic examination. Primary lymphosarcoma has not been described at this location in cows. Clinically it resembles chronic frontal sinusitis, and trephination may be necessary to differentiate the 2 diseases.