Although the translocation (8;21) is the single most common structural rearrangement reported in acute myeloblastic leukemia (AML), it is rarely seen in AML FAB type M5. We describe a case of a 51-year-old male with a diagnosis of acute monoblastic leukemia (AML M5b with hemophagocytic component) whose karyotype showed at (8;21)(q22;22). To our knowledge, this is the first report of this translocation in an AML M5b. The t(8;21) has been associated with a good prognosis, but our patient suffered a fast and fatal evolution.