From 1926 to 1984, 1200 patients with hyperparathyroidism were treated surgically at Massachusetts General Hospital (MGH). This series included 50 (4%) unusual cases that involved anomalous parathyroid locations or supernumerary hyperfunctioning parathyroid glands. In 42 cases the diseased glands were found in unusual locations: In three patients, glands were high in the neck behind the angle of the jaw; nine patients' glands were entirely encapsulated within the thyroid gland; and 30 patients required sternotomy for removal of mediastinal tumors. The eight remaining patients (as well as five of the mediastinal cases) had supernumerary hyperfunctioning glands. The three undescended parapharyngeal neoplasms, five of the cervical supernumerary tumors, and the majority of the mediastinal glands were associated with the thymus gland or thymic remnants. These glands appeared to arise from undescended parapharyngeal vestiges, partially descended parathymus remnants deposited along the path of developmental migration, or hyperdescended mediastinal inferior glands from branchial pouch III. The nine intrathyroid parathyroids were totally enclosed within the thyroid parenchyma. These appeared to arise from superior parathyroid glands that were trapped during fusion of the lateral wing portion from branchial pouch IV with the developing lateral lobes of the median thyroid primordium. Of these fifty cases, 39 patients had undergone a total of 60 previous operations (57 cervical and three mediastinal explorations) at MGH (16 patients) or other institutions (23 patients). In eleven patients the unusual hyperfunctioning gland was successfully identified at the time of the initial operation. Forty-four patients (88%) were surgically cured, as evidenced by eucalcemia. There were six patients with permanent hypoparathyroidism and none with persistent or recurrent hyperparathyroidism.