Although most pituitary adenomas behave in a purely benign fashion, microscopic invasion of the subjacent dura is very common, and clinically overt infiltration of the surrounding dura and bone is apparent at intraoperative inspection in about one third of cases. The factors governing invasive behavior remain unknown but are believed to be separate from those regulating cell proliferation. Histological features alone do not distinguish between benign, invasive, and malignant tumors of adenohypophyseal origin. Multiple attempts have been made to identify prognostic markers of aggressive behavior among these tumors. They include cytogenetic analysis of putative tumor suppressor genes or proto-oncogenes as well as immunohistochemical detection of cell-cycle specific antigens. At present, however, these analyses can neither distinguish the indolent pituitary adenoma from one that will pursue an invasive course, nor reliably predict the prognosis in individual patients.