The authors report their 3-year experience with the diagnosis of parathyroid lesions in primary hyperparathyroidism patients in a geographic area where the occurrence of endemic goiter is medium. Our study was aimed at prospectively assessing preoperative imaging results in these patients. The following imaging methods were used: high-definition and color-Doppler ultrasonography (US), double-tracer 201Thallium-99mTechnetium (T1/Tc) subtraction scintigraphy, Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and US-guided fine-needle aspiration of the suspected parathyroid lesions. Preoperative US and scintigraphy were performed in 50 patients with primary hyperparathyroidism; in addition, color-Doppler US studies were performed in 33 patients for vascular characterization of the lesions. In 19 patients, the suspected lesions were punctured under US guidance to measure parathormone (PTHa) and thyroglobulin (TGa) levels in the aspirated material. CT and MRI were performed in 9 patients, to identify a possible ectopic parathyroid gland. Surgery demonstrated 48 solitary parathyroid lesions and one double parathyroid adenoma. In one patient no abnormal parathyroid gland was found. Overall sensitivity rates of US and scintigraphy were 85.7% and 61.2%, respectively. In multinodular goiter patients, the sensitivity rates of US and scintigraphy were 71.4% and 47.6%, respectively. At color-Doppler US the presence of parenchymal vascularization was specific of parathyroid nodules and the method helped differentiate parathyroid lesions from thyroid nodules in 14 multinodular goiter patients. Overall PTHa sensitivity was 72.2% and its specificity 100%. Overall TGa sensitivity was 100% and specificity 94.7%. CT and MRI allowed the detection of 8 ectopic parathyroid lesions. In conclusion, in our personal experience, US should be preferred to double-tracer T1/Tc subtraction scintigraphy in the early examination of primary hyperparathyroidism patients. When US detects a suspected parathyroid lesion, color-Doppler US and PTH and TG sampling can make useful diagnostic tools for reducing false-positive results, especially when thyroid disease is associated.