BACKGROUND AND OBJECTIVES: Imatinib mesylate induces a complete cytogenetic response (CCR) in many patients with chronic myeloid leukemia (CML). However, the ultimate goal of therapy for CML is complete elimination of Philadelphia chromosome positive cells or BCR-ABL rearrangements. We studied molecular responses in CML patients in CCR after imatinib treatment. DESIGN AND METHODS: Real-time quantitative reverse transcriptase polymerase chain reaction analysis were used to monitor BCR-ABL levels in 59 CCR patients. Negative results were confirmed by two different techniques performed in two different laboratories. Patients were considered in complete molecular remission if they had four undetectable analyses from two separate samples taken three months apart. RESULTS: The median follow-up was 41 months (17-53). The median BCR-ABL/ABL ratio at the time of CCR was 0.3 % (0-9.88). Patients were split into two groups: group A (n=43) comprised patients with a detectable BCR-ABL/ABL ratio throughout the follow-up and group B (n=16) included those with an undetectable level of BCR-ABL/ABL (< 10(-5)) i.e. in complete molecular remission. No relapses were observed in group B, while 13 group A patients lost their CCR. The probability of losing CCR in this group was 33.2 % >+/-18.0. By Cox regression analysis the best factor for predicting the probability of achieving molecular remission was having a CCR at 6 months (p=0.038) or at 3 months (p=0.024). INTERPRETATION AND CONCLUSIONS: Molecular remission after imatinib treatment, i.e. BCR-ABL/ABL< 10-5 in peripheral blood, is not a rare event, particularly in patients achieving CCR at 6 months.