The hypercalcemia of hyperparathyroidism (HPT) can cause devastating effects to the patient and only surgical removal of the hyperfunctioning parathyroid tissue can definitely cure the disease. Radionuclide parathyroid imaging has no role in the diagnosis of hyperparathyroidism or in the selection of the type of treatment. However, once surgery is decided (99m)Tc-sestamibi scanning can localize abnormal parathyroid glands preoperatively. In primary HPT radionuclide assessment may occasionally be helpful before bilateral neck exploration, it can identify patients suitable for focused surgery and is a prerequisite of the minimally invasive radioguided parathyroidectomy. In secondary and tertiary HPT the clinical value of parathyroid scintigraphy remains debatable, but in persistent or recurrent disease this modality is a first line examination before reoperation. In conclusion, (99m)Tc-sestamibi assessment has a well defined clinical role in the surgical management of patients with primary hyperparathyroidism and in recurrent disease, but its usefulness in cases of secondary hyperparathyroidism is not clearly established.