Background: The gross tumor volume (GTV) definition for malignant pleural mesothelioma (MPM) is ill-defined. We therefore investigated which imaging modality is optimal: computed tomography (CT) with intravenous contrast (IVC), positron emission tomography-CT (PET/CT) or magnetic resonance imaging (MRI). Material and methods: Sixteen consecutive patients with untreated stage I-IV MPM were included. Patients with prior pleurodesis were excluded. CT with IVC, 18FDG-PET/CT and MRI (T2 and contrast-enhanced T1) were obtained. CT was rigidly co-registered with PET/CT and with MRI. Three sets of pleural GTVs were defined: GTV(CT), GTV(CT+PET/CT) and GTV(CT+MRI). Quantitative and qualitative evaluations of the contoured GTVs were performed. Results: Compared to CT-based GTV definition, PET/CT identified additional tumor sites (defined as either separate nodules or greater extent of a known tumor) in 12/16 patients. Compared to either CT or PET/CT, MRI identified additional tumor sites in 15/16 patients (p = .7). The mean GTV(CT), GTV(CT+PET/CT) and GTV(CT+MRI) [+/- standard deviation (SD)] were 630.1cm(3) (+/- 302.81), 640.23 cm(3) (+/- 302.83) and 660.8cm(3) (+/- 290.8), respectively. Differences in mean volumes were not significant. The mean Jaccard Index was significantly lower in MRI-based contours versus all the others. Conclusion: As MRI identified additional pleural disease sites in the majority of patients, it may play a role in optimal target volume definition.