Mantle cell lymphoma (MCL) is a rare but aggressive non-Hodgkin lymphoma subtype with a poor prognosis; most patients relapse despite initial response to therapy. Response was traditionally evaluated by computed tomography (CT), but the introduction of [(18)F]Fluorine-Deoxyglucose Positron Emission Tomography (PET) changed response assessment in aggressive lymphoma. However, the value of PET-evaluation in MCL has not been studied yet. Therefore, PET- and CT-findings were investigated in 37 patients with MCL (239 scans) and categorised following standardised response criteria for CT-evaluation (IWC-criteria), PET-evaluation (EORTC-criteria) and combined PET/CT-evaluation (IWC + PET-criteria). FDG-PET showed a high sensitivity for the detection of deposits of MCL and a higher FDG-uptake was shown in patients with the more aggressive blastoid-variant of MCL versus common MCL. However, routine use of PET for end-of-treatment response assessment in MCL cannot be recommended because CT- and PET-based designation systems had equivalent prognostic value. PET-based end-of-treatment response assessment only provided additional information over CT-based response assessment in a subpopulation of patients with highly FDG-avid MCL. PET allowed early detection of preclinical relapse during post-therapy surveillance, but the therapeutic consequences of such information are currently unclear.