A t(1;19)(q23;p13) is detected cytogenetically in approximately 5% of childhood acute lymphoblastic leukemias (ALLs) and its presence has been associated with an increased risk of relapse in several previously-completed Pediatric Oncology Group (POG) clinical trials. The t(1;19) fuses E2A to PBX1 in more than 95% of cases and this molecular abnormality can be reliably identified by polymerase chain reaction (PCR)-mediated amplification of E2A- PBX1 chimeric mRNAs. We used a nested PCR assay, which reproducibly detected a 104- to 105-fold dilution of t(1;19)+ into t(1;19)- cells, to evaluate minimal residual disease (MRD) in 48 children with t(1;19)+ ALL enrolled in POG clinical trials for lower (POG 9005) and higher (POG 9006) risk ALL. Peripheral blood (PB) and bone marrow (BM) samples were collected prospectively at the end of consolidation (weeks 25 and 31 after end of induction) and the presence or absence of PCR-detectable MRD was correlated with clinical outcome. Overall, 41 of 148 (28%) samples were PCR+. Of the 65 time points with informative results from both PB and BM, PCR results were concordant for 51 pairs (10 PB+/BM+, 41 PB-/BM-) and discordant for 14 (5 PB+/BM-, 9PB-/BM+), indicating that assessment of only PB or only BM can inaccurately classify some PCR+ cases as PCR-. There were no significant differences in event-free survival between PCR+ and PCR- patients. We conclude that qualitative detection of MRD by amplification of E2A-PBX1 chimeric mRNAs at the end of consolidation was not significantly predictive of outcome for children treated on POG 9005-9006 and that such results should not be used to alter therapy for patients with t(1;19)+ ALL.