Abstract Flow cytometry‐based immunophenotyping is a mainstay of diagnostics in acute myeloid leukaemia (AML). Aberrant CD56 and T‐cell antigen expression is observed in a fraction subset of AML cases, but the clinical relevance remains incompletely understood. Here, we retrospectively investigated the association of CD56 and T‐cell marker expression with disease‐specific characteristics and outcome of 324 AML patients who received intensive induction therapy at our centre between 2011 and 2019. We found that CD2 expression was associated with abnormal non‐complex karyotype, NPM1 wild‐type status and TP53 mutation. CD2 also correlated with a lower complete remission (CR) rate (47.8% vs. 71.6%, p = 0.03). CyTdT and CD2 were associated with inferior 3‐year event‐free‐survival (EFS) (5.3% vs. 33.5%, p = 0.003 and 17.4% vs. 33.1%, p = 0.02, respectively). CyTdT expression was also correlated with inferior relapse‐free survival (27.3% vs. 48.8%, p = 0.04). In multivariable analyses CD2 positivity was an independent adverse factor for EFS (HR 1.72, p = 0.03). These results indicate a biological relevance of aberrant T‐cell marker expression in AML and provide a rationale to further characterise the molecular origin in T‐lineage‐associated AML.