Purpose ETV6/RUNX1(+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables. Materials and Methods Sixty-three patients were diagnosed with ETV6/RUNX1(+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETI/6/RUNX1(+) fusion, and the presence of additional cytogenetic abnormalities. Results The 5-year event-free survival was 84.1 +/- 4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9 4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5 +/- 6.9%. Conclusion ETV6/RUNX1(+) ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end of remission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.