Certain molecular mutations are associated with signs of cell morphology and differentiation in acute myeloid leukemia (AML). However, only limited data are available for the detailed analysis of such correlations. In this study, AML patients were classified into 4 subsets according to CD34, HLA-DR and CD11c expression levels. Significantly low CD34 antigen expression was observed in nucleophosmin (NPM1)- mutated patients and in those with FMS- like tyrosine kinase 3 internal tandem duplication (FLT3- ITD). No correlations were observed among NPM1 mutations, FLT3- ITD and monocytic morphology in patients without CD34 expression. Both NPM1 mutations and FLT3- ITD were absent in cluster IIb patients (CD34+CD11c-). The associations among NPM1 mutations, FLT3- ITD and the surface molecular signature of leukemic cells may offer beneficial information about the pathogenesis of AML.