In spite of many advances in diagnosis and therapy, primary brain tumors remain a serious challenge for clinicians. In particular, high-grade gliomas are characteristically radioresistant and their localization and invasive growth pattern often reduce the effectiveness of surgery. MRI and CT scan proved powerful tool to diagnose primary brain tumors. Nevertheless, these methods have some limitations, especially after surgery and radiochemotherapy, in discriminating between residual neoplasia versus radionecrosis / scar tissue. Scintigraphy by MIBI and Tetrofosmin, successfully used as imaging agents in oncology (i.e. breast and lung cancer), was also applied in diagnosis and follow-up of brain tumors. These two radiotracers are synthetic lipophilic cationic complexes and their uptake and retention depend on perfusion and cellular metabolism so that the level of radiotracer uptake corresponds to the cellular activity of the tumor. Although these two radiopharmaceuticals present similar imaging properties, very few studies in brain tumors imaging were performed with Tetrofosmin. On the contrary, MIBI was widely proved useful in diagnosis of brain tumors, showing high specificity and sensitivity. A trend between MIBI uptake and gliomas grade was observed, while this relationship is not present in glioblastomas, which exhibit a variable uptake. Most important, MIBI was demonstrated effective in patients follow-up after treatments, well differentiating tumoral viable tissue versus radionecrosis. Since MIBI and Tetrofosmin are physiologically taken by intracranial structures like choroid plexus, the detection of small tumoral lesion in para-ventricular areas, especially in case of recurrence, may be problematic. In such cases, the dual integrated modality imaging system SPECT/CT might be considered of value to obtain a precise anatomical localization and to exclude the presence of disease in sites of physiologic tracer accumulation.