Translocations involving 21q22 are commonly observed in both de novo and therapy-related acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). They often result in the disruption of RUNX1 and give rise to fusion genes consisting of RUNX1 and different partner genes, which contribute to leukemogenesis. To date, at least 21 such translocations are known from the literature. Here we report two novel translocations involving the RUNX1 gene: t(1;21)(q12;q22) in a 53-year-old woman with AML-M5b and t(11;21)(q13;q22) in a 65-year-old man with AML-M2. The abnormalities revealed by R-banding karyotypic analysis were confirmed with interphase and metaphase fluorescence in situ hybridization (FISH), chromosome painting, and M-FISH.