Malignant Pleural Mesothelioma (MPM) is a relatively rare neoplasia characterized by a poor prognosis. Recent studies show that new therapeutic approaches can lead to an improvement in life quality and to a prolonged survival; therefore, proper evaluation of MPM before, as well as after, therapy, is needed. The aim of this study was to evaluate the impact of 18F-FDG photon emission tomography (PET) scan compared to computed tomography (CT) findings in patients affected by MPM, whether untreated or already treated. We studied 15 consecutive patients (13 male and 2 female) with a histological diagnosis of MPM, with a mean age of 69.9 years (range: 38-78 years old) and a recent total-body CT scan. Five (5) patients were studied for staging, while 10 patients were studied after therapy. An FDG PET scan was carried out 60 minutes after an intravenous (i.v.) injection of 370 MBq of 18F-FDG. For each patient, we compared the PET stage to the CT stage, and evaluated the role of PET in choosing a therapeutic approach. In 9 of 15 (60%) patients, there was no difference between the PET and the CT stage. In 2 of 15 (13%) patients, PET upstaged the disease, while in 4 of 15 (27%) patients PET downstaged MPM. According to these results, patient management was changed in 3 cases. Specifically, 1 patient was excluded from surgery, and 2 patients had different chemotherapy. These data suggest that PET is useful in the evaluation of MPM, giving additional data that can clarify doubtful CT findings, especially regarding lymph node involvement and distant lesions. In conclusion, FDG PET was found to play a worth-while role in patient management.