OBJECTIVE: Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG), a glucose analogue, as a metabolic tumour marker, has been proposed for the non-invasive staging of oncological disease. Tumours demonstrate increased glycolytic activity and thereby, FDG PET can differentiate benign from malignant lesions. To determine its role in the mediastinal staging of patients with suspected non-small cell lung cancer, a prospective study of FDG PET and computed tomography (CT) compared to surgery and pathology was performed. The analysis group consists of 50 patients, 37 men and 13 women, mean age 64 years (range, 41-78 years). METHODS: A nuclear physician, blind to the clinical and CT data, graded the FDG PET studies qualitatively on a five-point scale, based on the intensity of glucose uptake, for the presence of mediastinal nodal tumour involvement. Scores of four or greater were considered positive for tumour. An experienced radiologist interpreted the patients' CT scans blind to the other data. The CT criterion for tumour involvement was a nodal long axis diameter of 10 mm or greater. All patients underwent either thoracotomy or mediastinoscopy to obtain surgical specimens. The PET, CT, surgery and pathology were mapped according to the American Thoracic Society nodal classification resulting in 201 nodal stations evaluated. The imaging studies were analysed for N2 or N3 tumour involvement compared to histology or dissection of nodal stations. RESULTS: All patients had proven non-small cell lung carcinoma. PET excluded tumour in 175 of 181 nodal stations (specificity 97%) compared to 162 of 181 (specificity 90%) by CT. PET correctly identified 16 of 20 (sensitivity 80%) nodal stations with tumour compared to 13 of 20 by CT (sensitivity 65%). Overall, PET correctly staged 191 of 201 nodal stations (accuracy 95%) compared to 175 of 201 by CT (accuracy 87%). By the McNemar test, PET was significantly more specific than CT in excluding nodal tumour involvement (X2 = 5.5, P < 0.05). CONCLUSIONS: FDG PET is more specific than computed tomography in the non-invasive mediastinal staging of non-small cell lung cancer and has an important clinical role in the pre-operative staging of lung cancer patients.