Thirty-six adult patients with classical hyperparathyroidism had parathyroidectomy in which tissue evaluation included oil red O stains. Neutral lipid staining has been reported to distinguish hyperfunctioning parathyroid from suppressed or normal tissue. In normal glands, parathyroid chief cells show abundant coarse and fine intracytoplasmic neutral lipid droplets. In contrast, the cytoplasm of chief cells is essentially free of neutral lipid droplets in adcnomatous, hypcrplastic. or carcinomatous glands. This study shows that to limit or alter surgical exploration solely on the basis of the findings of the oil red O technique will lead to significant judgmental error (6/36 patients). Such errors are especially likely in the patient who has enlarged parathyroid glands containing a normal distribution of parenchymal to adipose tissue. There was excellent agreement between the clinical outcome, surgical-pathological findings, and the oil red O stain in 30 cases of parathyroid adenoma, nodular hypcrplasia, and a control group (12 patients) who had biopsies of normal parathyroid tissue during the course of thyroidectomy.