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Mantle cell lymphoma (MCL) is an aggressive lymphoma subtype with poor prognosis in which 18F-FDG-PET/CT role in treatment response evaluation and prediction of outcome is still unclear. The aim of this multicentric study was to investigate the role of 18F-FDG-PET/CT in staging MCL and the prognostic role of Deauville criteria (DC) in terms of progression-free survival (PFS) and overall survival (OS). We retrospectively enrolled 229 patients who underwent baseline and end-of-treatment (eot) 18F-FDG-PET/CT after first-line therapy. EotPET/CT scans were visually interpreted according to DC. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT for evaluation of bone marrow (BM) were 27%, 100%, 100%, 48% and 57%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT for evaluation of the gastrointestinal (GI) tract were 60%, 99%, 93%, 90% and 91%, respectively. At a median follow-up of 40 months, relapse occurred in 104 cases and death in 49. EotPET/CT results using DC significantly correlated with PFS, not with OS. Instead, considering OS, only MIPI score was significantly correlated. In conclusion, we demonstrated that MCL is an FDG-avid lymphoma and 18F-FDG-PET/CT is a useful tool for staging purpose, showing good specificity for BM and GI evaluation, but suboptimal sensitivity. EotPET/CT result was the only independent significant prognostic factor that correlated with PFS.