Thus, the presence of mutations in NPM1 or CEBPA was considered to indicate favorable prognosis, and the detection of internal tandem duplication (ITD) in FLT3 was assigned to the intermediate category, I. Thereafter, advances in molecular methodologies, mainly with Next Generation Sequencing (NGS) panels, allowed us to unravel the complexity of the molecular landscape of AML [5], leading to further refinement of AML risk categories by ELN in 2017 [6]. This evidence concerns the gene NPM1 and acute myeloid leukemia.