Umberto Vitolo, MD, Città della Salute e della Scienza University Hospital, Turin, Italy, discusses the unmet needs in the first-line treatment of diffuse large B-cell lymphoma (DLBCL), and how therapy in the frontline setting can be improved beyond the standard of care, R-CHOP. He highlights how the variety of distinct subtypes of DLBCL should be molecularly targeted. This interview took place at the 15th International Conference on Malignant Lymphoma (ICML), in Lugano, Switzerland.