In the last 10 to 15 years surgery of primary hyperparathyroidism (PHPT) moved from the wide bilateral neck exploration to various types of limited neck exploration ranging from unilateral neck surgery to minimally invasive approaches as the minimally invasive radioguided parathyroidectomy. In contrast with the bilateral neck exploration, an accurate preoperative localizing imaging, which is mainly based on (99m)TC-sestamibi scintigraphy, is mandatory when planning a concise parathyroidectomy. Following imaging criteria, only a fraction of PHPT patients accounting for approximately 60% to 70% of all PHPT patients can be eligible for a minimally invasive parathyroidectomy. Only PHPT patients with a high probability to be affected by a solitary parathyroid adenoma showing a high (99m)TC-sestamibi uptake and with a normal thyroid gland should be offer a minimally invasive radioguided parathyroidectomy. The (99m)TC-sestamibi SPECT technique and the double-tracer 123-iodine or (99m)TC-pertecnetate/(99m)TC-sestamibi scintigraphic technique are the most sensitive and accurate preoperative imaging modalities and their utilization is recommended when considering a minimally invasive radioguided parathyroidectomy. Two main intraoperative procedures for the minimally invasive radioguided surgery have been described: the single-day protocol and the different-day protocol. In the single-day protocol a 740 MBq dose of (99m)TC-sestamibi is injected to the patient, scintigraphic imaging is obtained by dual-phase technique and then the patient is operated on within approximately 3 hours from radio-tracer injection. In the different-day protocol, a double-tracer parathyroid scintigraphy is obtained some days before surgery with the aim of better planning the type and extension of intervention. The day of intervention, for the purpose of radioguided surgery only, a low 37 MBq dose of (99m)TC-sestamibi is injected to the patient in the operating theatre a few minutes before the start of intervention. The main advantages of minimally invasive radioguided parathyroidectomy over the traditional wide bilateral neck exploration can be resumed as follows: a shortening in the operating and recovery time, possibility of local anesthesia, possibility of ambulatory surgery or same-day discharge, less postsurgical hypocalcemia, less postsurgical pain, favourable cosmetic results, benefits from a cost-analysis point of view.