BACKGROUND: Positron emission tomography (PET), a new noninvasive imaging modality, utilizing 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG), has demonstrated increased FDG uptake in lung tumors. OBJECTIVE: To determine the diagnostic efficacy of PET-FDG imaging in differentiating benign from malignant solitary pulmonary nodules. PATIENT SELECTION: A prospective study of 30 patients who presented with indeterminate solitary pulmonary nodules less than 3 cm in size based on chest radiograph and computed tomographic (CT) scan. SETTING: Two tertiary care medical centers in Omaha, Neb: Creighton University Medical Center and the Omaha Veterans Administration Medical Center. MEASUREMENTS: Positron emission tomographic imaging of the lung was performed 1 h after intravenous injection of 10 mCi of F-18-FDG. Qualitative analysis of the images was performed independently by two observers by visual identification of the areas of increased FDG uptake in the lung nodules. Semiquantitative analysis was performed using computation of differential uptake ratio (DUR). Histologic specimens were obtained in 29 patients (thoracotomy 20, transthoracic needle aspiration biopsy 8, bronchoscopy 1). RESULTS: Positron emission tomographic imaging correctly identified 27 of 30 pulmonary nodules. Diagnostic accuracy was high with sensitivity of 95 percent and specificity of 80 percent. The positive and negative predictive value of PET imaging for solitary pulmonary nodules was 90 percent and 89 percent, respectively. The DUR values were significantly higher for malignant nodules (mean +/- SD, 5.55 +/- 2.79) than benign nodules (mean +/- SD, 0.95 +/- 0.99) (p < 0.001). There was one false-negative result in a patient with a 1-cm nodule identified as a scar adenocarcinoma. There were two false-positive cases and both had caseating granulomas with active inflammation and Histoplasma organisms. CONCLUSION: PET-FDG imaging of the lung, a new noninvasive diagnostic test, has a high degree of accuracy in differentiating benign from malignant pulmonary nodules. PET-FDG imaging could complement CT scanning in the evaluation and treatment of patients with solitary pulmonary nodules.