Nineteen patients with histologically diagnosed supratentorial cerebral neoplasms carried out CT and/or MRI, 201T1 SPECT and 99mTc-HM-PAO studies preoperatively. 99mTc-HM-PAO SPECT images revealed information about both tumoral perfusion and intracellular concentration of mediators converting 99mTc-HM-PAO to hydrophilic derivates (glutathione and other yet unknown factors) within viable tumoral cells while 201T1 SPECT images about permeability, extension of tumoral capillary network and viable tumoral cells presence. Basing on the different mechanisms of the tracer uptake, cerebral supratentorial tumors could be distinguished in three groups: 1) cerebral tumors presenting 201T1 very high uptake (201T1 index > 1.5) and homogeneous and high retention of 99mTc-HM-PAO (CBI > or = 1.05) (meningiomas, PRL adenoma); histologically these neoplasms presented very rich neoformed capillary network; 2) cerebral neoplasms with 201T1 high uptake (201T1 index > 1.5) and with inhomogeneous retention of 99Tc-HM-PAO (high grade gliomas amd metastasis); microscopically these tumors presented vascular proliferation, necrosis and high cellularity; 3) cerebral neoplasms characterized by 201T1 low uptake (201T1 index < 1.5) and lower retention of 99Tc-HM-PAO than cerebellum (low grade gliomas); at microscopic examination these neoplasms were characterized by absence of vascular proliferation and necrosis. These results suggest coupled 201T1/99Tc-HM-PAO SPECT is necessary to discriminate intra-axial from extra-axial tumor localization (lacking CT or MRI) and to detect the grade of malignancy of gliomas and tumor cell presence within necrotic areas.