Imatinib mesylate therapy leads to major or complete cytogenetic response in the majority of patients with CML in the chronic phase. A subset of these patients also achieves remission at a molecular level. It is not known if such patients will require continuous therapy, or whether imatinib could be safely discontinued. This report describes divergent clinical outcomes in two patients with chronic phase CML who discontinued imatinib therapy after obtaining a molecular remission; one patient who maintained a complete molecular response throughout a period of interruption, and a second patient with overt relapse, highlighting the uncertainty of discontinuing imatinib therapy.