Primary hyperparathyroidism is a common entity that routinely lends itself to prompt surgical cure. Infrequently, multiple surgical explorations are required to effect a cure. A case is reported of a 27-year-old man with hypercalcemia and nephrocalcinosis. The initial surgical exploration failed to identify the abnormal parathyroid tissue. Hypercalcemia necessitated rigorous antihypercalcemic therapy; three subsequent operations, including a mediastinal exploration, were unsuccessful. On the fifth exploration, which took barely an hour, a 35-g adenoma was removed from the left superior posterior mediastinum. This report illustrates that a detailed knowledge of the possible locations of aberrant parathyroid tissue and the skills of the operating surgeon are the sine qua non for those patients requiring one or more parathyroid reexplorations.