Reports on the use of the real-time quantitative polymerase chain reaction (RQ-PCR) for childhood acute promyelocytic leukemia (APL) therapy are scarce. This study describes the prognostic significance of quantification of the PML-RARa transcript in children with APL. Since January 2004, we have analyzed 40 children treated with all-trans-retinoic acid ± arsenic trioxide in induction. Thirty-nine patients (97.5%) entered complete remission. The 5-year rates of disease-free survival (DFS) and overall survival in these patients were 73.1 and 91.4%, respectively. By employing a standardized RQ-PCR protocol for minimal residual disease (MRD) monitoring, we determined that less than 1 normalized copy number (NCN) after induction indicates higher probability of a more favorable treatment outcome. After induction therapy, thirteen out of 38 (34.2%) patients in hematologic remission showed a negative RQ-PCR result (less than 1 NCN), which was correlated with the lower probability of relapse (100 and 55.2% DFS at 5 years in the negative and positive RQ-PCR groups, respectively; P = 0.018). PML/RARa-based MRD monitoring by RQ-PCR may allow us to identify subgroups of patients at low risk of relapse after induction.