Nine de novo DLBCL cases (n=150) carry both TP53 mutation and MIR34A methylation (“double hit”) and these patients have an exceedingly poor prognosis with a median survival of 9.4 months (P<0.0001), while neither TP53 mutation, MIR34A or MIR34B/C promoter methylation alone (“single hit”) influence on survival. Here, MIR34B is linked to diffuse large B-cell lymphoma.