Sequential molecular and cellular changes during remission induction were investigated in a case of acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA). By means of clonality analysis, the assessment of the retinoic acid receptor alpha gene alterations, as well as conventional cytologic studies, it was demonstrated that remission induction of APL by ATRA proceeds in two steps: first, the differentiation of the leukemic clone to mature granulocytes and its subsequent extinction; second, proliferation/differentiation of the residual normal clones to restore polyclonal hematopoiesis.