Patients with hyperparathyroidism who have not had previous neck surgery do not require preoperative localization because of the high success rate of cervical exploration (95%) and the limited sensitivity and specificity of all imaging modalities currently in use. Successful parathyroid exploration requires knowledge of the normal and frequently encountered variations in parathyroid anatomy (Fig. 4). Experience permits recognition of often subtle multiple gland disease. In skilled surgical hands, results are excellent with minimal morbidity. When recurrent or persistent disease or previously operated patients are encountered, confirmation of the diagnosis and attempts at localization should precede operation. Technetium sestamibi SPECT imaging and ultrasonography with FNA of suspicious glands are complementary tests that are readily available, inexpensive, and well tolerated by patients. If these tests are unsuccessful, MRI, CT, and invasive procedures should be pursued until the gland is localized.