Etoposide is a semi-synthetic, topoisomerase active podophyllotoxin derivative which frequently causes deletions and rearrangements on chromosomes 11q23 and 11q22. It can cause therapy-related, acute myeloblastic leukemia in patients receiving the drug in a schedule-dependent manner. Here we present a case with acute lymphoblastic leukemia who developed secondary acute myeloblastic leukemia 28 months after the beginning of therapy which contained etoposide on an every-other-week schedule.