The Philadelphia chromosome (Ph) appears as a secondary change at the onset of disease. However, a late-appearing or secondary Ph has also been observed in rare cases of chronic myeloid leukemia and even more unusual events of acute myeloid leukemia. We recently experienced a 63-year-old female patient with the M1 subtype of acute myeloid leukemia. Cytogenetic studies revealed t(3;3)(q21;q26) as the primary change and the Ph translocation as the additional (secondary) anomaly. These findings further support the conclusion that the Ph plays a role not only in multistep leukemogenesis but also in clonal evolution related to disease progression.