A 56-year-old man was referred to our hospital for an abnormal chest X-ray shadow. He had no apparent experience of occupational exposure to asbestos. A chest computed tomography (CT) scan revealed irregular pleural thickening and no pleural effusion in the right thoracic cavity. Positron-emission tomography with ¹⁸F-fluorodeoxyglucose (FDG-PET)/CT scan on admission showed no significant FDG accumulation on the thickened pleura. The pleural biopsy was done surgically, and the histopathological diagnosis of the resected specimen was a mixed-type malignant pleural mesothelioma. A right extrapleural pneumonectomy was performed and followed by chemotherapy using cisplatin combined with pemetrexed. Malignant mesothelioma generally shows pleural thickening and pleural effusion in a CT scan and FDG uptake in FDG-PET/CT. We reported here a case of pleural thickening with false-negative PET images and no pleural effusion that requires a surgical pleural biopsy for the differential diagnosis of malignant mesothelioma from inflammatory pleural thickening.