BACKGROUND We retrospectively studied the results of diagnostic imaging using 3 different modalities to determine their usefulness for preoperative localization of the parathyroid, and whether accurate preoperative localization information could be used to modify the surgical approach for parathyroidectomy in patients with primary hyperparathyroidism. METHODS Images of 37 parathyroid adenomas or hyperplasias in 35 patients with primary hyperparathyroidism were obtained using ultrasonography, computed tomography, and subtraction scintigraphy (using thallium 201 [thallous chloride] and either iodine 123 or technetium 99m pertechnetate [99mTcO4-]). RESULTS Approximately three fourths of the adenomas or hyperplasias were successfully identified by ultrasound (76.7%) and computed tomography (76.4%), even when the weight of the tumor was less than 500 mg. However, subtraction scintigraphy was of limited use (61.3% successfully identified). A combination of these modalities gave excellent results for detecting adenomas and hyperplasias, leading to an accurate prediction rate of 96.0%. CONCLUSIONS We conclude that using the combination of these 3 imaging modalities is very useful for the detection of parathyroid adenomas and hyperplasias, and that with such accurate localization information, the unilateral approach alone, or even simple excision of the parathyroid tumors might be feasible, enabling less invasive surgical treatment.