Clear morphological criteria for differentiating benign from malignant parathyroid tumors are not yet available and unfavorable prognosis cannot be predicted by histopathological parameters alone. A retrospective study of a series of parathyroid lesions was designed to evaluate the diagnostic role of the cell cycle-associated Ki-67 antigen detected by MIB-1 monoclonal immunocytochemistry. The mean tumor proliferative fraction (TPF), expressed as the number of Ki-67-positive nuclei per 1,000 cells, was 0.8 in normal parathyroid glands (nine specimens), 26.0 in hyperplasias (11 specimens), 32.8 in adenomas (11 specimens), and 60.5 in a group of tumors with histological features consistent with carcinoma (12 specimens). The difference between the latter two values was statistically significant (P < .05). When the five most clinically aggressive tumors were considered, the difference was even more remarkable (TPF, 78.6; P < .001). Oncocytic and pleomorphic cell components were found to proliferate with a labeling pattern similar to that of the chief cells. We conclude that proliferative activity is an additional useful parameter for evaluating parathyroid tumors diagnostically. Aggressive behavior may be expected in those tumors with a TPF greater than 6%.