Most hyperfunctioning parathyroid tumors situated in the mediastinum can be removed by means of a cervical approach. However, a few tumors, because of their location deep in the chest, require mediastinotomy for removal. These tumors are probably derived from parathyroid glands that have developed from the third branchial pouch. Between 1942 and 1980, 38 such tumors were removed at the Mayo Clinic, using a sternum-splitting procedure. With one exception, the patients had undergone previous parathyroid exploration, Almost all of the patients had significant complications of primary hyperparathyroidism (HPT). Thirty-seven patients (97%) were cured after removal of their mediastinal parathyroid tumors, but postoperative chest complications were encountered in eight patients (21%), and eight have permanent hypoparathyroidism. Six patients had selective arteriography, two had selective thyroid venous sampling and parathyroid hormone assay, and 13 had mediastinal computed tomography in an attempt to localize tumors before operation. The anatomic locations of the tumors at operation were variable, but the vast majority (68%) were in or near the thymus.