To study the stability of lineage commitment of acute promyelocytic leukemia (APL) cells, we treated freshly isolated leukemic cells from the patients with APL with various differentiation-inducers. APL cells showed granulocytic differentiation when treated with all-trans retinoic acid as previously reported. We showed here that freshly isolated APL cells could be also induced to differentiation to monocytic/macrophagic lineage with inducers such as 1,25 dihydroxyvitamin D3,12-O-tetradecanoylphorbol-13-acetate or tumor necrosis factor-α. These results suggest that APL cells have the capacity to differentiate toward not only granulocytic lineage but also monocytic/macrophagic macrophagic lineage. It is not clear that these results indicate the lineage promiscuity of normal promyelocytes or lineage infidelity of APL cells. However, these data provide an important clinical implication, because a possible therapeutic efficacy of using differentiation-inducing agents toward monocytic/macrophagic lineage in the remission induction therapy for the patient with APL or salvage therapy for the resistant APL cases to all-trans retinoic acid therapy is suggested.