The ultrastructural features of 69 parathyroid glands from 43 patients with hyperparathyroidism were studied to distinguish between different parathyroid lesions causing hyperparathyroidism. Samples came from 44 cases of hyperplasia, 21 of adenoma, 3 of carcinoma, and 1 from a histologically normal gland. To establish the diagnosis we took into account intraoperative findings during surgery as well as light microscopic examination. Ultrastructural features, evaluated on a semiquantitative scale, were correlated with diagnostic, clinical, and biochemical parameters. Neoplastic glands were heavier than nonneoplastic ones, and carcinomatous glands were heavier than adenomatous glands. Our findings suggest that the cellular membrane of adenomatous glands shows more folding than that of hyperplastic glands, mainly in the capillary pole. Carcinomatous glands show the greatest degree of irregularity, with the formation of microvilli-like projections. Hyperplastic glands, in turn, are richer in glycogen deposition. Secretory granules appear in higher amounts when the serum calcium level is high. These findings are not of diagnostic value by themselves, but they can be taken in consideration to aid in differential diagnosis.