Molecular monitoring can detect residual disease during many years of imatinib therapy. There are an estimated 10¹² leukemic cells present at diagnosis of CML. The Philadelphia chromosome remains detectable by cytogenetic analysis until the leukemic cells decline by approximately 2 logs, which occurs at an estimated median of 6 months of imatinib. Therefore, the Philadelphia chromosome may never be detectable beyond 6 months in a substantial number of patients. However, we have found that BCR-ABL1 transcripts remain detectable in approximately half of the patients for 6 years and molecular monitoring continues to track the leukemic cell decline. The limit of detection of BCR-ABL1 by RQ-PCR is reached when the leukemic cells decline approximately 4.5-5 logs.