We report here the first case of acute myelomonocytic leukemia (AMMoL) with both t(8;12)(q13;p13) and t(11;19)(q23;p13.1). A 75-year-old woman was initially diagnosed as having AMMoL with t(11;19) (q23;p13) as a sole abnormality. At the second relapse, G-banding analysis of the bone marrow cells showed 46,XX,t(11;19)(q23;p13)/46,XX,t(8;12)(q13;p13),t(11;19)(q23;p13). Fluorescence in situ hybridization analysis with chromosome-specific painting probes confirmed both the der(8)t(8;12) and the der(12)t(8;12). Reverse transcription-polymerase chain reaction analysis detected the MLL/ELL fusion transcript, indicating that the breakpoint on chromosome 19 was 19p13.1. Leukemic cells at the second relapse were positive for CD2, CD13, CD33, and CD34 but negative for CD14 and HLA-DR. The patient died within 2 months after a subclone with t(8;12)(q13;p13) had appeared. In the literature, t(8;12)(q12;p13) has been observed in two cases of myelodysplastic syndrome and one case of acute myeloblastic leukemia. Our results indicated that t(8;12)(q13;p13) may be one of the recurrent aberrations in myeloid malignancies, although molecular heterogeneity of the breakpoints might exist. Furthermore, it is suggested that t(8;12)(q13;p13) may play an important role in the progression of the disease and lead to the poor prognosis.