A 40-year-old male with Ph-positive CML underwent PBSC autografting after initial treatment with hydroxyurea and interferon. Following autograft he remained in chronic phase with cytogenetic or molecular evidence of low levels of residual Ph-positive cells. However, additional cytogenetic abnormalities, including t(3;21) typically seen in therapy-related myelodysplastic syndrome (MDS) and AML and blast crisis of CML, developed as an independent cell line following the autograft. More than 4 years after the autograft, the patient remains in chronic phase with no evidence of accelerated phase or blast crisis of CML, but with a concurrent MDS. We report a case of CML who developed therapy-related MDS following PBSC autograft while still remaining in chronic phase.