To undertake an evaluation of histopathological variables in parathyroid carcinoma, 95 cases with this diagnosis were collected from 37 hospitals. Two tumor categories emerged from a review of tissue sections and follow-up information: 56 cases demonstrating extraglandular invasiveness or tumor recurrence were classified as definitive carcinomas, whereas 39 tumors lacking these criteria were classified as equivocal cases. Several morphological variables other than invasiveness differed between the two groups: Fibrosis, necrosis, nuclear atypia (especially macronucleoli), and mitotic figures were significantly more frequent in the carcinoma group. These variables also showed a positive correlation with an aberrant DNA pattern demonstrated by image cytometry. The triad macronucleoli, more than five mitoses per 50 high-power fields, and necrosis were associated with an aggressive behavior in terms of recurrent disease. A minority of the carcinomas had a bland cytologic appearance and differed from benign lesions only by their invasiveness. Certain patterns of fibrosis and necrosis were common but neither pathognomonic nor constant features of malignancy. Mitotic activity constituted a prognostic risk factor but was of limited diagnostic significance. In half of the carcinomas, the frequency of mitoses did not exceed values recorded in benign parathyroid lesions.