Increased tumor uptake of (18)F-fluorodeoxyglucose (FDG) measured by positron emission tomography (PET) reflects glucose metabolism and proliferative activity of tumor cells. We conducted a study to assess the usefulness of FDG-PET for early prediction of the response to gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), in advanced non-small cell lung cancer (NSCLC). Five NSCLC patients underwent FDG-PET to evaluate changes in FDG uptake at day 2 and 4 weeks after the initiation of gefitinib therapy compared with FDG-PET prior to therapy. FDG uptake was evaluated as the maximum standardized uptake value (SUVmax) of the target lesions, which were assessable by conventional CT. Based on the CT evaluation, two patients exhibited a partial response (PR), two patients had stable disease (SD) with a minor response, and one patient had progressive disease (PD). In patients with PR and SD, SUVmax decreased by 61+/-18% (standard deviation) and 59+/-12%, respectively, on day 2, and by 26+/-6 and 43+/-10%, respectively, at 4 weeks after the initiation of gefitinib. Two patients with SD had decreased FDG uptake within 2 days of initiation of therapy, and achieved progression-free survival (PFS) of more than 12 months. In contrast, SUVmax increased up to 153+/-21% at 2 days and 232+/-73% at 4 weeks in a patient with PD. The present preliminary study suggests that FDG-PET may be able to predict response to gefitinib in the early stage of therapy in patients with advanced NSCLC and may have a potential prognostic role.