We set out to determine the accuracy in predicting the success of biochemical and localizing studies for use in a minimally invasive parathyroidectomy. Preoperative sestamibi scans, intraoperative gamma-probe examinations, and intraoperative PTH (IOPTH) monitoring were performed on a prospective cohort of patients. Seventy-one patients were included in the study. Of the 59 patients (83%) with primary HPT, adenoma localization by sestamibi scanning was correct in 95% with solitary adenomas, but was correct in only 25% of the 14 patients with multiple adenomas. In patients with secondary and tertiary disease, sestamibi scanning incorrectly identified a single hot spot in 64% of cases. In no case of hyperplasia was the probe useful in locating other glands after a single gland was removed. IOPTH was accurate in 78% of patients with primary disease and in only 45% of patients with nonprimary disease. A minimal approach can be considered in a select group of patients that does not have familial primary HPT, secondary or tertiary disease, coexisting thyroid pathology, or an equivocal sestamibi scan. Only patients with a positive single hot spot on sestamibi scan can be considered candidates. Using this criteria only 64% of all patients with hyperparathyroidism are candidates for a minimally invasive approach. The combination of a solitary hot spot on sestamibi scan and a fall in IOPTH allows the surgeon to make the correct decision regarding the need to convert to a bilateral approach in 93% of these selected patients.