A 7-year-old, intact male standard Poodle dog with hypothyroidism and atypical hyperadrenocorticism developed acute signs of lethargy, weakness, inappetence, vomiting, and diarrhea. Clinical signs progressed to hind limb proprioceptive deficits, aggressive behavior with obtundation, and an equivocal seizure. Necropsy revealed a mass in the sellar region that histologically consisted of multinucleated giant cells, macrophages, and hemosiderin-laden macrophages with fewer lymphocytes and plasma cells admixed with large regions of cholesterol cleft deposition, fibrin, and prominent Rosenthal fibers. Pituitary tissue was not identified on gross or histologic examination, but the mass was partially bordered by epithelial cells. The histologic characteristics are similar to changes described in the human medical literature as xanthogranuloma of the sellar region and xanthogranulomatous hypophysitis.