Recent histopathologic evidence challenges the teaching that enlargement of a solitary parathyroid gland is invariably caused by an adenoma, whereas multiple gland enlargement results from hyperplasia. We have re-examined the parathyroid tissue obtained from 152 consecutive patients undergoing surgery for primary hyperparathyroidism and compared it with their clinical outcome. Our approach was to excise enlarged glands and biopsy the remainder. In 124 patients (82%) at least three glands were biopsied or removed. The ratio of adenoma to hyperplasia was reversed by our histologic re-examination; adenomas were found in only 27 patients (25 single, two double), whereas hyperplasia was found in 117 patients (one gland, 87 patients; two glands, 16 patients; three glands, five patients; four glands, nine patients). Normal tissue only was reported in eight patients. During a 2-year follow-up, five patients (3%) developed hypocalcemia and none developed recurrent hypercalcemia. Our results indicate that a full neck exploration with removal of all enlarged glands is more important than the histologic diagnosis in planning a successful surgical strategy for primary hyperparathyroidism.