At the 2014 American Society of Hematology (ASH) Annual Meeting, Prof Christian Gisselbrecht (St. Louis Hospital, Paris, France) discusses the molecular approach in managing diffuse large B-cell lymphoma (DLBCL). The molecularly defined DLBCL subtypes, germinal centre B-cell-like (GCB)-DLBCL and activated B-cell-like (ABC)-DLBCL, have important clinical implications.