The AML1/ETO fusion gene is expressed in virtually all patients with t(8;21)(q22;q22) acute myelogenous leukemia (AML). Long-term complete remission (CR) of AML with t(8;21) has been observed despite the presence of residual AML1/ ETO fusion transcripts, although detection may depend on the sensitivity of the methods used. We examined a patient with recurrent AML who showed the t(8;21)(q22;q22) chromosomal abnormality following a CR of 15 years. The blast cells at the time of recurrence expressed the AML1/ETO fusion transcript, and the breakpoint of the AML1 gene was located on intron 5. Southern blot analysis of the DNA extracted from bone marrow slides that had been made and stored for 15 years revealed the same rearrangement pattern of the AML1 gene. Furthermore, the junction sequences between the AML1 and the ETO genes, analyzed by long-distance inverse polymerase chain reaction, proved to be completely identical. These findings can be interpreted in two ways: (1) The initial leukemia clone persisted and finally relapsed after 15 years in the dormant state. (2) AML developed in different subclones having the same AML1/ETO junctional sequences but with additional genetic changes (second hit).