Magnetic resonance imaging (MRI) and computed tomography (CT) may not be reliable in the differential diagnosis of tumour necrosis, scar and recurrent tumour. We compared 201Tl-chloride SPET with CT and MRI for the differential diagnosis of these cerebral lesions. Brain SPET was performed in 40 patients after the intravenous injection of 201Tl-chloride. All 40 patients also had a CT or MRI scan, and a histological diagnosis was available for 27 of the patients. For each patient, the ratio of counts in the lesion region of interest (ROI) to counts in the contralateral ROI was calculated and found to be between 0.58 and 9.60. The ratios for high-grade gliomas, metastases and meningiomas were high (> 2.7), especially in tumours with good vascularization. A low ratio (< 1.7) was noted in patients with low-grade astrocytoma, necrosis or ischaemic lesions. There were two exceptional cases of ischaemic lesions in the luxury perfusion stage (ratios of 3.61 and 3.87), as verified by HMPAO-SPET. We found that 201Tl-chloride SPET helps to differentiate between malignant tumours, poorly vascularized benign lesions and necrosis. Differentiation between low-grade astrocytoma and non-malignant lesions was not possible, but there was a trend towards differentiating between low-grade astrocytoma and ischaemic infarction. The timing of the investigation is important to avoid false-positive results in hyperperfused ischaemic tissue.