TP53 mutation can occur in several World Health Organization AML subtypes based on the disease ontogeny and morphology. However, the clinical behavior of AML bearing TP53 mutation appears to reflect its underlying genetic features rather than the AML category into which the disease falls. TP53-mutated AML cases with favorable or intermediate-risk karyotype, a single mutation with intact copy number status, low variant-allele fraction, and lacking an abnormal pattern of p53 protein expression by immunohistochemistry display a more favorable prognosis; conversely, the specific type of TP53 mutation does not appear to influence prognosis. t-AML, therapy-related AML; MRC, with myelodysplasia-related changes; NOS, not otherwise specified; RGA, recurrent genetic abnormalities. Professional illustration by Somersault 18:24.