Following radiation therapy for brain tumors, patients often have clinical deterioration due to either radiation necrosis or recurrent tumor progression in the treatment field. The distinction between these entities is important but difficult clinically or even with CT or MRI. T1-201 has been known to accumulate in various tumors and be useful to grade, predict prognosis or detect recurrence of glioma. The aim of this study was to evaluate the usefulness of T1-201 SPECT in the differentiation of recurrent tumor from radiation necrosis. Of 67 patients who did T1-201 brain SPECT imaging with clinically suspected recurrent tumor or radiation necrosis, 20 patients underwent histopathological examination and constituted the study population. T1-201 uptake indices on T1-201 brain SPECT imaging were calculated and correlated with histopathological diagnosis. Of 20 patients, 15 were histopathologically confirmed as recurrent original tumor or malignant transformation of benign tumor and 5 were diagnosed as radiation necrosis. On T1-201 SPECT, 18 of 20 had T1-201 index above 2.5 which was regarded as positive indicator for the presence of tumor. Seventeen cases showed concordance, which consisted of 15 true positive and 2 true negative. Discordant 3 cases were all false positive. There was no case of false negative. The sensitivity, specificity, positive and negative predictive value of T1-201 SPECT were 100%, 40%, 83% and 100%. In conclusion, T1-201 brain SPECT is a sensitive diagnostic test in the detection of recurrent tumor following radiation therapy and is useful in the differentiation of recurrent tumor from radiation necrosis. Relatively low specificity should be evaluated further in larger number of patients in consideration of sampling error and referral bias for pathologic examination.