The aim of this study was to evaluate positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) for the staging of non-small cell lung cancer (NSCLC) before combined neoadjuvant, i.e. preoperative, radio-chemotherapy (RCT). From November 1998 until September 2001, 101 patients with NSCLC were investigated prospectively. The inclusion criterion was a histologically proven NSCLC of stage IIIA or B according to conventional staging including biopsy. The results of PET were compared with those obtained by mediastinoscopy, computed tomography (CT), bone scan and abdominal ultrasonography. Validation of discrepant findings was achieved by biopsy or repeated CT. PET proved to be highly accurate for the detection of lymph node metastases (sensitivity 96%, specificity 73%, positive predictive value 88%, negative predictive value 89%, accuracy 88%) as well as distant metastases (in 25/101 patients, all previously unknown). PET findings changed further treatment in 29/101 patients (29%). Twenty-five were excluded from RCT due to the presence of previously unknown distant metastases. One patient was free of metastases and therefore was operated on without pre-treatment. Two patients did not receive any further treatment because a malignant tumour could be excluded after PET. In the final patient PET demonstrated a tumour pattern not typical for NSCLC which could be attributed to a seminoma after repeated biopsy. FDG PET is the most accurate non-invasive diagnostic procedure for the staging of advanced NSCLC. Therefore use of FDG PET is highly recommended in order to select patients for neoadjuvant or other stage-dependent treatment modalities.