ABSTRACT We analyzed mutations in four genes (FLT3, KRAS/NRAS, and PTPN11) that might disrupt the Ras/MAPkinase signaling pathway, to evaluate their prognostic value in children younger than 16 years-old with B-cell-precursor acute lymphoblastic leukemia (Bcp-ALL). The overall survival (OS) was determined with the Kaplan-Meier method. MAPkinase-genes were mutated in 25.4% and 20.1% childhood and infant Bcp-ALL, respectively. Children with hyperdiploidy were more prone to harboring a MAPKinase genes mutation (OR 3.18; 95% CI 1.07-9.49). The mean OS of overall cases was 54.0 months. FLT3 and PTPN11 mutations had no impact on OS. K/NRAS mutations were strongly associated with MLL-AFF1 (OR 5.78; 95% CI 1.00-33.24), and conferred poorer OS (P=0.034) in the univariate analyses.