The aim of this study was to assess the feasibility of PET/CT for chemotherapy response evaluation in patients with malignant pleural mesothelioma (MPM). Among the 50 patients with MPM who had been treated from January 2007 through May 2010, we compared the response evaluation between conventional CT (modified RECIST-based evaluation) and FDG-PET (metabolic response: MR), before and after three cycles of therapy. Of these 50 patients, 38 were classified as stable disease by CT evaluation (modified RECIST). Moreover, in addition to evaluation of metabolic response with FDG-PET for them of CT-SD, they can be classified into 3 groups (PET-PR: 9, PET-SD: 16, and PET-PD: 13). Metabolic response (MR) was significantly correlated to median time-to-tumor progression (TTP) with a median TTP for metabolic responders (PET-PR+SD) of 17.6 months versus 10.7 months for nonresponders (PET-PD) (p<0.0161). Patients with an MR had a trend toward longer overall survival. FDG-PET is showing promise as an additional evaluation method. The use of FDG-PET in the assessment of chemotherapy response evaluation in MPM is highly predictive of patient outcome and may be useful for the decision of surgical procedure whether EPP or P/D. Our observations need to be validated in a larger prospective series.