In the past decade an increasing number of reports described recurrent gain-of-function mutations of NOTCH1 and NOTCH2 in lymphoproliferative disorders of the B series, including chronic lymphocytic leukemia (CLL), mantle cell (MCL), splenic marginal zone (SMZL), diffuse large B cell (DLBCL) and follicular (FL), Burkitt's (BL) and Hodgkin's (HL) lymphomas. The gene discussed is NOTCH1; the disease is mantle cell lymphoma.