The difference in 201Tl-chloride (201Tl) accumulation on single photon emission computed tomography (SPECT) between 58 benign (58 cases) and 48 malignant (46 cases) thoracic lesions, each of more than 20 mm in diameter was investigated. In the 34 benign and 48 malignant lesions depicted in both early (15 min) and delayed (3 h) images there was no significant difference in the mean early and delayed uptake ratios of lesion to normal contralateral lung between benign and malignant. However, the retention index in the lesion derived from (delayed ratio — early ratio)/(early ratio) ± 100% showed a significant difference (benign −4.30 ± 13.6% versus malignant 23.3 + 18.9%, P < 0.01), indicating the poor 201Tl retention in the benign lesions. Using the criteria of nondepiction in the delayed image or a negative retention index, 81.1% accuracy and 95.2% predictive value for diagnosis of benign lesions were obtained. Thus, 201Tl SPECT appears to have potential usefulness in the diagnosis of benign thoracic lesions.