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PURPOSE A morphofunctional approach to the management of brain tumours has been claimed to increase diagnostic accuracy. Among the proposed single-photon emission tomography (SPET) tracers, (99m)Tc-sestamibi is able to distinguish recurrent tumour from radio-necrosis and to identify early response or resistance to chemotherapy. Major drawbacks of sestamibi, that is, poor morphological resolution and the sites of physiological uptake, could be overcome by dual-modality, integrated systems. The purpose of this study was to investigate the real usefulness of (99m)Tc-sestamibi SPET/computed tomography (CT) and to establish a semiquantitative index. METHODS Charts from 33 consecutive patients selected for surgery, who underwent preoperative SPET/CT and magnetic resonance imaging (MRI), were reviewed. Tumours were confirmed histologically after the surgery in all patients and classified according to WHO recommendations. Semiquantitative indexes were obtained on images (maximum likelihood expectation maximization reconstructed) with and without attenuation correction and visual analysis of SPET versus SPET/CT was performed. RESULTS A significant statistical difference was shown between SPET and SPET/CT in terms of the delineation of medial shift, oedema and the ability to distinguish tumour from the skull-meninges complex and plexus. With regard to semiquantitative indexes, a ratio obtained comparing counts/pixel derived from a region of interest in the tumour area with mirrored region of interest in the contralateral site revealed a sensitivity of 90.9% and specificity of 71.45% in discriminating WHO grade 4 gliomas from a lower grade. CONCLUSION SPET/CT can distinguish tumour from the skull and other sites of physiological uptake better than SPET alone (as confirmed by MRI in all cases) and affords a morphological map. The proposed semiquantitative index also seems promising in identifying higher-grade disease. SPET/CT thus seems a useful additional tool in brain tumour management, especially when MRI is not feasible or PET/CT is not available.