CONTEXT: The sellar region is the site of frequent pathology. The pituitary is affected by a large number of pathologic entities arising from the gland itself and from adjacent anatomical structures including brain, blood vessels, nerves, and meninges. The surgical pathology of this area requires the accurate characterization of primary adenohypophysial tumors, craniopharyngiomas, neurologic neoplasms, germ cell tumors, hematologic malignancies, and metastases as well as nonneoplastic lesions such as cysts, hyperplasias, and inflammatory disorders. OBJECTIVE: To provide a practical approach to the diagnosis of pituitary specimens. DATA SOURCES: Literature review and primary material from the University of Toronto. CONCLUSIONS: The initial examination requires routine hematoxylin-eosin to establish whether the lesion is a primary adenohypophysial proliferation or one of the many other types of pathology that occur in this area. The most common lesions resected surgically are pituitary adenomas. These are evaluated with a number of special stains and immunohistochemical markers that are now available to accurately classify these tumors. The complex subclassification of pituitary adenomas is now recognized to reflect specific clinical features and genetic alterations that predict targeted therapies for patients with pituitary disorders.