Hypophysitis can present clinically as a mass lesion of the sella turcica. Secondary hypophysitis occurs in cases where a definite etiologic agent or process inciting the inflammatory reaction can be identified. In contrast, primary hypophysitis refers to inflammation confined to the pituitary gland with no identifiable etiologic associations. We report three cases of primary hypophysitis to illustrate the spectrum of three clinicopathological entities that encompass this disease: lymphocytic hypophysitis, granulomatous hypophysitis, and xanthomatous hypophysitis. Our three patients underwent surgery, with variable response. However, conservative, supportive treatment with or without surgical decompression is generally favored over aggressive and extensive surgical resection that results in hypopituitarism. We conclude that the optimal management of patients with hyophysitis requires a high index of suspicion before extensive surgical resection. Histological confirmation of the diagnosis of hypophysitis can be obtained by performing a biopsy or by requesting an intraoperative frozen section consultation.