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Secondary leukemia occurring after hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) is rare. Secondary AML usually follows autologous and not allogeneic transplants. When a new leukemia develops in a patient successfully treated with an allogeneic HSCT, the possibility of a de novo or secondary leukemia from either the donor or recipient should be considered. We present a case initially diagnosed as de novo AML without a cytogenetic abnormality. The patient was successfully treated with an HLA-matched sibling allogeneic HSCT. However, more than six years later, AML developed again and was associated with new complex cytogenetic abnormalities. After a second HSCT, the patient has been followed without serious complications. Considering the allogeneic setting, the newly developed cytogenetic abnormalities, a relatively long latent period, and the good clinical course after the second allogeneic HSCT, this case might represent a second de novo AML following successful treatment of the first AML. (Korean J Intern Med 2010;25:110-113)