Abstract: Objective To investigate whether fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) combined with thin-section CT improves the diagnostic performance for solitary pulmonary nodules (SPNs). Methods A total of 267 patients underwent examinations with 18F-FDG PET/CT and thin-section CT for evaluating the SPNs with undetermined nature, which was further confirmed by pathological examination or clinical follow-up. The performance of two diagnostic criteria based on findings in PET/CT alone (Criterion 1) and in PET/CT combined with thin-section CT (Criterion 2) were compared. Results Thin-section CT provided greater diagnostic information for SPNs in 84.2% of the patients. Compared with Criterion 1, the diagnosis based on Criterion 2 significantly increased the diagnostic sensitivity (80.4% vs 91%, P<0.01) and accuracy (76.4% vs 87.2%, P<0.01) for lung cancer. The lesion size and the CT features including lobulation, air bronchogram, and feeding vessel, but not SUVmax, were all helpful for characterizing non-solid SPNs. Thin-section CT rectified diagnostic errors in 50% (20/40) of the cancerous lesions, which had been diagnosed as benign by PET due to their low metabolism. For non-solid SPNs, Criterion 2 showed a significantly higher diagnostic sensitivity than Criterion 1 (90.0% vs 40.0%, P=0.000) but their diagnostic specificity were comparable (75.2% vs 58.3%, P=0.667). For solid nodules, the use of thin-section CT resulted in no significant improvement in the diagnostic performance (P>0.05). Conclusion The combination of PET/CT and thin-section CT creates a synergistic effect for the characterization of SPNs, especially non-solid nodules.