Objective: The aim of this work was to study the clinicopathological features of cases with primary hyperparathyroidism (PHPT) referred to National Cancer Institute (NCI), Cairo University in the last six years and to study the role of nuclear medicine techniques in the initial diagnosis and preoperative localization directing surgical management of these cases. Methods: This study included 27 patients with PHPT properly diagnosed and treated in the NCI, Cairo University from January 2005 to December 2010. Preoperative neck U/S and Tc-99m-MIBI scintigraphy were done in all cases. If preoperative localization detected a single lesion, unilateral exploration was done. Bilateral exploration was done if multiple foci of active parathyroid glands or no lesions were detected. Results: This study included 27 patients (8 males and 19 females). The median age was 43 years (range from 19 to 68 years). All cases presented with bone disease in the form of bony pain in 23 patients, bony swellings in 15 patients and pathological fractures in 6 cases. Twenty one patients (77.8%) had single adenoma, 5 cases (18.5%) had parathyroid hyperplasia, and only one case had double adenomas. The sensitivity of neck U/S in detecting single adenoma was 61.9% (13/21), with 81% positive predictive value (PPV) while the sensitivity of Tc-99m- MIBI scintigraphy was 90.5% (19/21) with 100% PPV. Based on preoperative localization tests, unilateral exploration was done in 19 patients with solitary adenomas. All cases in this group were cured with no reported case of persistent or recurrent hypercalcemia. Conclusion: Presentation of PHPT may mimic malignant bone tumors but fortunately these patients were correctly diagnosed with bone scan which confirm the presence of metabolic bone disease rather than bone metastases. This was followed by estimation of serum calcium and parathormone levels for confirmation. Unilateral exploration based on the combination of ultrasound and preoperative localization by Tc-99m-MIBI scintigraphy was effective and could replace the standard bilateral neck exploration in cases with solitary adenoma. Bilateral neck exploration was required for suspected bilateral disease, hyperplasia or non visualized parathyroids.