Purpose: Thallim-201 (201Tl) brain SPECT, which can represent cellular activity of brain lesions, may provide more useful information in differentiating between benign and malignant brain lesions more so than CT or MRI, that merely represents anatomic changes or breakdown of blood brain barrier. We used 201Tl brain SPECT prospectively to evaluate the utility of 201Tl-indices as an indicator of benign or malignant lesions. Materials and Methods: We studied 28 patients. There were 13 cases of benign lesions (3: nonspecific benign lesion, 3: meningioma, 2: low grade glioma, 1: tuberculoma, central neurocytoma, hemangioblastoma, radiation necrosis, and choroid plexus papilloma) and 15 cases of malignant lesions (6: glioblastoma multiforme, 5: anaplastic glioma, 2: medulloblastoma, 1: metastasis and lymphoma). In all patients, CT and/or MRI were obtained and then 201Tl brain SPECT was obtained with measuring mean 201Tl index and peak 201Tl index. An unpaired t-test was performed to compare the 201Tl-indices and pathologic diagnoses to evaluate the utility of 201Tl-indices as an indicator of benign or malignant lesions. Results: There were no statistically significant difference in 201Tl-indices between benign and malignant brain lesions (P>0.05). Conclusion: These results demonstrated that we could not use 201Tl indices on brain SPECT alone as an indicator of benign or malignant brain lesions.