A 37-year-old man with acute myelomonocytic leukemia (AML) M4E who exhibited the complex karyotype of 5q-, 7q-, and +22 in addition to inv(16), relapsed soon after complete remission. As previously reported, AML M4E carrying inv(16) is associated with a good prognosis, even when co-occurring with chromosomal abnormalities, which alone are considered to have poor outcome. Cytogenetic prognosis studies, such as CALGB or SWOG, have reported that certain additional chromosomal abnormalities or complex karyotypes might affect the prognosis of patients with AML M4E with inv(16). Our case suggests that, in general, AML M4E carrying inv(16) is in the favorable risk category, while cases with additional chromosomal abnormalities or complex karyotypes might be classified in the poor risk group and thus should be given additional clinical attention.