By combining pharmacological, molecular, and lipidomic approaches, we demonstrate that the ABC-DLBCL subtype in particular displays a phenotype suggestive of high ROS burden and adaptive lipid targeted anti-oxidant defense characterized by high expression of core ferroptosis regulators, including FSP1, GCH1, and a MUFA enriched lipidome. This evidence concerns the gene AIFM2 and aneurysmal bone cyst.