PURPOSE: Recently Tc99m MIBI (methoxyisobutylisonitrile) has been described as an alternative to thallium for localizing parathyroid lesions. The purpose of this study was to compare the efficacy of a Tc99m MIBI scan with a Tl201/Tc99m subtraction scan for localizing parathyroid lesions in patients with primary hyperparathyroidism. METHODS: Among 31 cases of primary hyperparathyroidism operated on at the Department of Surgery, Seoul National University Hospital from January 1997 to June 2001, a Tl201/Tc99m subtraction scan was performed on 16 patients and a Tc99m MIBI scan on 22 patients. Seven patients underwent both. RESULTS: The pathology was a single adenoma in 28 patients, a hyperplasia in 1 patient and a carcinoma in 2 patients. Hypercalcemia was controlled postoperatively in all cases. The sensitivities of the Tl201/Tc99m subtraction scan and Tc99m MIBI scan were 53.3% and 86.4%, respectively. The positive predictive values were 100% of the two study groups. CONCLUSION: We concluded that the better accuracy, superior image quality and lower cost of Tc99m MIBI scan will make it the new radiopharmaceutical parathyroid scan of choice. A unilateral approach can be used with a high degree of success, as in case of a preoperatively localized single parathyroid adenoma, which was confirmed when surgical exploration identified of a normal ipsilateral gland.