Chromosomal translocations at t(1;22)(p13;q13) have been reported to occur in a number of infants with acute megakaryoblastic leukemia. A set of female twins with acute megakaryoblastic leukemia are reported with this unique translocation of 1p13 to 22q13. The twins presented at 2 months of age with fever and poor feeding and subsequently developed progressive hepatosplenomegaly. One twin died before treatment could be started; the other became septicemic 5 days after initiation of chemotherapy and eventually died.