Primarily because of the lack of highly accurate preoperative localizing studies, the standard operation for primary hyperparathyroidism (HPTH) has consisted of bilateral neck exploration with examination of all four parathyroid glands. Recent experience with the technetium-99m-Sestamibi scan at our hospital has suggested that this single test was now accurate enough to allow unilateral neck exploration. This study was designed to examine the efficacy and safety of minimally invasive parathyroid-ectomy in select patients with a single adenoma demonstrated on a preoperative sestamibi. Eighteen consecutive patients with primary HPTH in whom a sestamibi scan suggested a single adenoma underwent unilateral neck exploration through a 2.5-cm incision, which was extended as necessary. Results were compared to the preceding 25 parathyroid explorations for primary HPTH due to a single adenoma, which were nondirected and included bilateral neck exploration. All patients undergoing minimal exploration were found to have a single adenoma and demonstrated a normal serum calcium within 24 hours of surgery. Standard bilateral exploration failed to locate the adenoma in one patient requiring subsequent re-exploration. Operative time, incision length, and length of hospital stay were all significantly less for those undergoing minimal exploration (all P < 0.01). There were no complications in either group. Minimally invasive neck exploration is a safe and effective treatment for primary HPTH, is easily accomplished under local anesthesia, and is associated with significant reductions in operative time and hospital stay. Limited exploration provides a better cosmetic result while decreasing the potential complications of bilateral exploration, but is dependent upon a high-quality sestamibi scan.