['The aim of the study was to define the cost-effectiveness of whole-body (18)F-FDG PET, as compared with chest CT, in screening for distant metastases in patients with head and neck squamous cell carcinoma (HNSCC).', 'In a multicenter prospective study, 145 consecutive patients with high risk factors for distant metastases and scheduled for extensive treatment underwent chest CT and whole-body (18)F-FDG PET for screening of distant metastases. The cost data of 80 patients in whom distant metastases developed or who had a follow-up of at least 12 mo were analyzed. Cost-effectiveness analysis, including sensitivity analysis, was performed to compare the results of (18)F-FDG PET, CT, and a combination of CT and (18)F-FDG PET (CT + (18)F-FDG PET).', 'Pretreatment screening identified distant metastases in 21% of patients. (18)F-FDG PET had a higher sensitivity (53% vs. 37%) and positive predictive value (80% vs. 75%) than did CT. CT + (18)F-FDG PET had the highest sensitivity (63%). The average costs in the CT, (18)F-FDG PET, and CT + (18)F-FDG PET groups amounted to euro38,558 (approximately $57,705), euro38,355 (approximately $57,402), and euro37,954 (approximately $56,801), respectively, in the first year after screening. CT + (18)F-FDG PET resulted in savings between euro203 (approximately $303) and euro604 (approximately $903). Sensitivity analysis showed that the dominance of CT + (18)F-FDG PET was robust.'] Are chest CT and whole-body 18F-FDG PET cost-effective in screening for distant metastases in head and neck cancer patients?