A case of acute myeloid leukemia (AML) with an unusual phenotype which was negative for a panel of myeloid antigens determined by flow cytometry, but was strongly positive for myeloperoxidase has recently been reported. We herein describe a case of AML with this unusual phenotype at diagnosis; relapse occurred with the acquisition of CD13 and CD33 expressions. Morphological features of the blasts at relapse seemed to be more compatible with myeloblasts than those at diagnosis. These phenotypic and morphological changes are suggestive of asynchronous differentiation, clonal evolution or clonal change of leukemic cells.