In the present report, we address the question if the reduction of standard dosage of imatinib mesylate (IM) in imatinib-intolerant chronic myeloid leukemia (CML) patients with undetectable residual disease may impair their outcome. Four patients are described. The median follow up from the beginning of IM therapy was 35 months (33-59). The median duration of real-time quantitative polymerase chain reaction (RQ-PCR) negativity on IM 200 mg daily was 17 months (4-37). We hypothesize that in IM intolerant CML patients with complete molecular remission, the compound dosage might be safely reduced to a lower than standard dose without to lose the response. A tight molecular monitoring of such patients should be required.