B-lymphoblastic leukemia (a.k.a. precursor B-cell acute lymphoblastic leukemia) is a heterogeneous disease at the clinical, morphologic, immunophenotypic and genetic levels. Recurrent genetic abnormalities in B-lymphoblastic leukemia with prognostic significance are well known and specifically delineated in the WHO 2008 classification (eg hyperdiploidy, t(9;22)(q34;q11.2); BCR-ABL1, t(12;21)(p13;q22); ETV6-RUNX1). In recent years, a subgroup of B-lymphoblastic leukemia with the recurring genetic alteration of RUNX1 amplification has emerged. This subgroup has a low incidence (2%) and an increased risk of relapse and overall worse outcome. Given these apparently distinctive clinicopathologic features, we evaluated eight cases of pediatric B-lymphoblastic leukemia with RUNX1 amplification treated on Children's Oncology Group protocols from 2000-2009. Compared with 25 consecutive B-lymphoblastic leukemia cases without RUNX1 amplification, we identified a trend toward male predominance (P-value=0.082) and low white blood cell count at presentation (P-value=0.081) in B-lymphoblastic leukemia with RUNX1 amplification. Older age at presentation was significant (median age 9.5 years, P-value=0.006). There was no significant difference in the presence of central nervous system disease, CD20 or myeloid antigen positivity on the blasts or percent circulating blasts in B-lymphoblastic leukemia with RUNX1 amplification versus other B-lymphoblastic leukemia types. Seven of eight patients (88%) are alive and free of disease at the time of last checkup (mean 50 months, range 14-116 months). Although we see a relatively good outcome in our small cohort of patients, recent findings from the Children's Oncology Group on a large set of patients suggests otherwise that these patients may have an inferior outcome compared with patients with B-lymphoblastic leukemia without RUNX1 amplification. Long-term follow-up in larger cohorts including minimal residual disease correlation is required.