We report a case of acute myelogenous leukemia (AML) with MLL (myeloid-lymphoid leukemia or mixed-lineage leukemia) gene rearrangement after exposure to tegafur/uracil. Cytogenetic and clinical findings in this patient: t(11;17) (q23;q25), AML-M4 morphology, development of AML within a short latent period after first exposure to tegafur/uracil, and good response to remission induction chemotherapy but short remission duration, have been considered typical features of therapy-related acute myelogenous leukemia (t-AML) after exposure to topoisomerase II-targeting agents. This case report suggests that t-AML may develop after exposure to tegafur/uracil and that MLL gene rearrangement may not necessarily be specific to t-AML after exposure to topoisomerase II-targeting agents.