To evaluate prospectively the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) with use of fluorodeoxyglucose (FDG), compared with that of stand-alone CT, for the preoperative staging of non-small cell lung cancer, with surgical and histologic findings used as the reference standard. Institutional review board approval and patient informed consent were obtained. From November 2003 to February 2004, 106 patients (78 men, 28 women; mean age, 56 years) with non-small cell lung cancer underwent curative surgical resection (tumor resection and lymph node dissection) after stand-alone CT followed by integrated FDG PET/CT. Tumor stages were determined by using the TNM and American Joint Committee on Cancer staging systems. Histopathologic results served as the reference standard. Statistically significant differences in tumor staging between integrated PET/CT and stand-alone CT were determined with P < .05 obtained by using the McNemar test or with a generalized estimating equation. The primary tumor was correctly staged in 84 patients (79%) at stand-alone CT and in 91 patients (86%) at integrated FDG PET/CT (P = .25). For the depiction of malignant nodes, the sensitivity, specificity, and accuracy of CT were 70% (23 of 33 nodal groups), 69% (248 of 360), and 69% (271 of 393), respectively, whereas those of PET/CT were 85% (28 of 33), 84% (302 of 360), and 84% (330 of 393) (P = .25, P < .001, and P < .001, respectively). There were 112 false-positive interpretations at CT for 54 hilar, 16 subcarinal, 29 paratracheal, 10 subaortic, and two pulmonary ligament nodal groups and one upper paratracheal group, compared with only 58 false-positive interpretations at PET/CT for 32 hilar, seven subcarinal, 13 lower paratracheal, and six subaortic nodal groups. There were 10 false-negative interpretations at CT for four hilar, two lower paratracheal, and two subcarinal nodal groups, one prevascular and retrotracheal group, and one inferior pulmonary group, but only five false-negative interpretations at PET/CT (one each for paratracheal, subaortic, subcarinal, inferior pulmonary, and hilar nodal groups). Integrated FDG PET/CT is significantly better than stand-alone CT for lung cancer staging and provides enhanced accuracy and specificity in nodal staging.