The clinical course of Mantle Cell Lymphoma (MCL) varies between individual patients. Early detection of risk is crucial to assign MCL patients to novel treatment strategies. Most of the established biomarkers of outcome require specifically trained pathologists or molecular analysis. Here we introduce MAIPI (MCL Artificial Intelligence Prognostic Index), a deep learning algorithm trained only on Hematoxylin and Eosin (H&E) images of diagnostic biopsies of n = 428 MCL patients from clinical trials to assess prognosis. The capability of MAIPI to predict disease outcome was validated in an independent cohort of n = 140 patients treated with immunochemotherapy with and without ibrutinib. MAIPI selects areas of interest by itself and provides prognostic information independent of the MCL International Prognostic Index (MIPI) and Ki67 and without the need of molecular testing or expert pathologists evaluation.