A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was which diagnostic modality [computed tomography (CT), positron emission tomography (PET), combination PET/CT and magnetic resonance imaging (MRI)] provides the best diagnostic and staging information in patients with malignant pleural mesothelioma (MPM). Overall, 61 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that fluorodeoxyglucose (FDG)-PET is superior to MRI and CT but inferior to PET-CT, in terms of diagnostic specificity, sensitivity and staging of MPM. Four studies reported outcomes using FDG-PET to diagnose MPM. PET diagnosed MPM with high sensitivity (92%) and specificity (87.9%). Mean standardised uptake value (SUV) was higher in malignant than benign disease (4.91 vs. 1.41, P<0.0001). Lymph node metastases were detected with higher accuracy (80% vs. 66.7%) compared to extrathoracic disease. Three studies assessed the utility of PET-CT to diagnose MPM. Mean SUV was higher in malignant than benign disease (6.5 vs. 0.8, P<0.001). MPM was diagnosed with high sensitivity (88.2%), specificity (92.9%) and accuracy (88.9%). PET-CT had low sensitivity for stage N2 (38%) and T4 (67%) disease. CT-guided needle biopsy definitively diagnosed MPM after just one biopsy (100% vs. 9%) much more often than a 'blind' approach. CT had a lower success rate (92% vs. 100%) than thoracoscopic pleural biopsy but was equivalent to MRI in terms of detection of lymph node metastases (P=0.85) and visceral pleural tumour (P=0.64). CT had a lower specificity for stage II (77% vs. 100%, P<0.01) and stage III (75% vs. 100%, P<0.01) disease compared to PET-CT. Overall, the high specificity and sensitivity rates seen with open pleural biopsy make it a superior diagnostic modality to CT, MRI or PET for diagnosing patients with MPM.