Objectives: 201Tl - chloride, 99mTc - MIBI, 99mTc(V) - DMSA SPECT has been used in distinguishing lung cancer from benign lesion. To compare the diagnostic efficacy of SPECT with these tumor - seeking agents, we performed three consecutive SPECT using 201Tl, 99mTc - MIBI, 99mTc(V) - DMSA in same subjects with a solitary pulmonary lesion. Methods: SPECT was carried out at 10min and 3hr for 201Tl after injection of 2 mCi, and 2hr for 99mTc - MIBI and 99mTc(V) - DMSA after injection of 20mCi, respectively, in 37 patients with a solitary pulmonary lesion(27 lung cancer and 10 benign diseases). In patients showing visual uptake on lesion site, we obtained the lesion - to - bakground(target lesion/contralateral normal lung) uptake ratio from transverse slice for each radionuclide and also calculated the retention index for 201Tl. Results: The diagnostic sensitivity of 201Tl, 99mTc - MIBI and 99mTc(V) - DMSA SPECT to lung cancer was 100%, 96% and 73%, and the specificity was 40%, 70% and 70%, respectively. The low specificities for these agents were mainly due to high positive uptake in patients with active pulmonary tuberculosis. There were no significant differences in uptake ratios and retention index between malignant and benign lesions, and among the histologic types of lung cancer Conclusion: 201Tl and 99mTc - MIBI showed higher sensitivity than 99mTc(V) - DMSA for detecting lung cancer, but was of limited usefulness in distinguishing lung cancer from benign lesion due to low specificity, especially in area with a high prevalence of active pulmonary tuberculosis.