Background: Despite the success of CNS preventive therapy in reducing the incidence of CNS recurrence, CNS relapse remains a significant cause of treatment failure in ALL. There is no single factor or group of factors that can predict with absolute certainty the risk of CNS relapse. Aim of the study: The objective of the current retrospective study is to analyze the experience of pediatric oncology unit - Faculty of Medicine - Cairo University, with cases of CNS relapse in children with ALL. Material and Methods: The files of all children with ALL, in the period between January 1995 and December 1999, are reviewed. Disease status at presentation and treatment protocols are correlated with disease free period, site of relapse, and overall survival. Results: The study included 86 children, 55 males and 31 females. CNS disease at presentation was present in 2 patients (2.3%). According to age and initial leukocytic count, patients are stratified into: standard risk 39 patients, and high risk 47 patients. Out of the 66 evaluable patients that received induction therapy, 89.4% achieved complete remission. The induction mortality rate was 10.6%. Disease-free and overall 5-year survival is 56% and 68% respectively. Five-year survival rate for standard risk group is 75%, while 5-year survival rate for high risk group is 59%. Relapse rate was 47.1%. CNS relapse was observed in 4 cases (7.8%). Statistically, there was no significant difference between the relapsed and maintained remission groups. Conclusion: Egyptian patients are usually presented with poor prognostic factors. More accurate risk classification should be attempt for better selection of patients and assessment of treatment outcomes. Intensification of induction and consolidation treatment should be considered as well as improving supportive measures.