Acute myeloid leukemia (AML) is a heterogenous hematologic neoplasm characterized by recurrent cytogenetic and molecular abnormalities resulting in arrested differentiation and proliferation of immature hematopoietic precursors. Risk stratification in AML remains the principle in survival prognostication and treatment selection. Prognostication of AML has relied mostly on cytogenetics for a long time. In recent years, many gene mutations have emerged as prognostic relevant, initially in patients with normal karyotype and then regardless of cytogenetics. The most relevant cytogenetic and molecular abnormalities are included within the current European LeukemiaNet (ELN) guidelines. The approach to AML in 2023 differs greatly from that of 10 years ago. Improved pathophysiological and genomic understanding has led to newly approved therapies. This study evaluated outcomes between the 2010, 2017 and 2022 ELN criteria in twelve patients aged ≥18 years with newly diagnosed AML. The age patients ranged from 18 to 76 years (median, 33 years). Our data set included results of karyotype analyses and next-generation sequencing (NGS) assays targeting recurrently mutated genes in myeloid malignancies and gene fusions. Karyotype analysis identified abnormalities in five patients (41.7%) and normal karyotype in two patients (16.6%). Five patients did not have a karyotype result, due to culture failure or lack of medical request. Molecular abnormalities occurred in 100% of patients (mutations in 16 genes, fusions involving RUNX1 and KMT2A). Overall survival ranged from 0.2 to 28.3 months (mean, 10.6 ± 8.4 months). ELN 2010 categorized as adverse three patients (25.0%). ELN 2017 and ELN 2022 categorized as risk adverse seven (58.3%) and five (41.7%) patients, respectively. Most patients with ELN 2022 adverse-risk disease were older 60 years. Compared with ELN 2017 criteria, the ELN 2022 changed the assigned risk in 16.7% of patients from adverse to intermediate risk. Updates to the ELN 2022 guidelines include removal of FLT3-ITD allelic ratio and NPM1 comutation status with subsequent allocation of FLT3-ITD into the intermediate-risk group. These changes were responsible for these risk reclassifications. There was consensus on the favorable risk classification for the three versions of the ELN. The ELN 2010, 2017 and 2022 guidelines categorized as risk intermediate 50%, 16.7% and 33.3% of patients, respectively. Patients with ELN 2022 adverse–risk AML had genetic abnormalities associated to poor prognosis, as complex karyotype, -7, KMT2A rearranged and, mutations in RUNX1, EZH2 and U2AF1. Advances in AML biology have led to an increasing complexity in prognostic estimation. This study showed the contribution of genetic abnormalities to risk stratification in AML. Consistent with prior analyses, certain ELN defining mutations and cytogenetic abnormalities were correlated with adverse prognosis.