Single photon emission tomography (SPET) represents an indispensable diagnostic tool in nuclear medicine. Due to better contrast resolution, cross sectional and 3D images, SPET plays a useful complementary tool to bidimensional planar scintigraphy in certain clinical conditions, while representing the procedure of choice in others. However, high resolution SPET with pinhole collimator (P-SPET) can improve conventional SPET sensitivity with parallel hole collimators. This review summarizes data on the employment of conventional SPET and P-SPET in breast cancer, differentiated thyroid cancer (DTC) and hyperparathyroidism patients, using the cationic lipophilic complexes [(99m)Tc]metoxy isobutyl isonitrile (sestaMIBI) and [(99m)Tc]tetrofosmin as oncotropic radiotracers. In breast cancer patients, SPET with these radiotracers can play an important complementary role to planar scintimammography in detecting primary tumors, especially when non palpable and small in size, whereas SPET and particularly P-SPET represents the procedure of choice in preoperative axillary lymph node status evaluation in which planar is almost always irrelevant. In DTC follow-up patients, SPET and P-SPET with cationic lipophilic radiotracers are indicated in both locoregional and distant metastasis detection, especially in patients with high Tg serum levels and negative radioiodine scanning in whom these procedures represent a reliable alternative to diagnostic (131)I scanning. Moreover, the combined use of [(99m)Tc]tetrofosmin P-SPET and US can identify recurrences and lymph node metastases in the neck, both fixing and non fixing iodine, downstaged or negative at (131)I scanning. SPET can also be a useful complementary tool to planar parathyroid scintigraphy in the detection and localization of small and ectopic parathyroid adenomas in the neck or mediastinum, while neck P-SPET seems to also significantly increase planar sensitivity in hyperplastic glands. SPET and P-SPET are indicated in persistent and recurrent hyperparathyroidism including from carcinoma.