Tc-99m tetrofosmin (Tc-99m TF) is a myocardial perfusion agent. We investigated the potential role of Tc-99m TF for the imaging of lung cancers in comparison to thallium-201 (T1-201). Sixteen patients with histologically proven malignant lesions and five patients with benign (infectious) lesions of the lung were studied using a same-day protocol. Planar images were obtained 15 minutes after injection of 2-3 mCi T1-201 and 20 and 60 minutes after injection of 20-25 mCi Tc-99m TF. Visual and semi-quantitative analyses were performed to evaluate the localization of activity in the radiologically demonstrated lesion in comparison to the contralateral normal lung. Visually, all malignant lesions but two demonstrated moderate-to markedly increased uptake of both tracers similarly. Lesion boundaries and central necrotic areas were better defined on most of the Tc-99m TF images. In malignant lesions, the lesion/contralateral normal lung activity ratios were 1.38±0.16 and 1.47±0.21 (mean±SD) on T1-201 and Tc-99m TF studies, respectively. In benign lesions, these ratios were 1.17±0.21 and 1.26±0.27. The differences in mean ratios of malignant and benign lesions were statistically significant for both tracers (p<0.025 for T1-201, p<0.05 for Tc-99m TF). We conclude that tumor avidity of Tc-99m TF is similar to that of T1-201 in lung cancers and may be useful in the diagnosis and follow-up of lung tumors.