PurposeTo compare the utility of Tc-99m MIBI SPECT and Tl-201 chloride SPECT for presurgical assessment of lung cancer mediastinal lymph node metastases.MethodsForty-one patients with non–small-cell lung cancer underwent dual-isotope imaging with Tl-201 chloride and Tc-99m MIBI and were evaluated for mediastinal lymph node involvement.ResultsThe sensitivity rates of early and delayed Tc-99m MIBI SPECT and of early and delayed Tl-201 chloride SPECT for detecting mediastinal nodal metastases were 69%, 69%, 92%, and 92%, respectively. The corresponding specificity rates were 96%, 96%, 93%, and 96%.ConclusionTl-201 chloride SPECT is superior to Tc-99m MIBI SPECT when used to detect mediastinal lymph node metastases in patients with non–small-cell lung cancer.