Nucleophosmin gene (NPM1) mutations characterize acute myeloid leukaemia (AML) with normal karyotype and frequently co-exist with FLT3 internal tandem duplications (ITD). We evaluated bcl-2, bax, NPM1 and FLT3-ITD in 222 AML patients. Bax/bcl-2 ratio >0.35 and NPM1 without FLT3-ITD were significantly associated (P = 0.0001). NPM1-mutated (mt)/FLT3-ITD negative patients showed a higher complete remission (CR) rate (90%, P = 0.0002) and a longer overall survival (OS, P = 0.00007). NPM1-mt/FLT3-ITD negative plus bax/bcl-2 > 0.35 subset showed a very high CR rate (96%), very long OS (P = 0.00005) and disease-free survival (P = 0.004). The favourable prognosis of NPM1-mt/FLT3-ITD negative patients might be explained by a higher bax/bcl-2 ratio.