Children with Down syndrome (DS) are at an increased risk of developing acute leukemia. Acute myeloid leukemia predominates among DS children below 4 years of age but acute promyelocytic leukemia (APL) has rarely been reported in DS. Acute myeloid leukemia in DS is extremely sensitive to treatment but the optimum treatment of de novo or relapsed APL in DS is not known. We describe a child with DS and APL, who despite having a multiply relapsing course, achieved a third remission with ATRA and chemotherapy, which is sustained with maintenance therapy. A brief review of literature is also presented.