In this article, we present the unusual case of early death in a child with a FLT3-ITD positive CBFB-MYH11 rearranged AML, characterized by trio-filtered Whole Exome Sequencing (WES) analysis, and a comparison to available published data, to foster the identification of molecular determinants of disease aggressiveness in this case. This evidence concerns the gene CBFB and acute myeloid leukemia.