Background: Acute leukemia, including both myeloid and lymphoblastic are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemia cells in the central nervous system (CNS) and the subsequent formation of brain tumors. Methods: This is a prospective study of acute leukemia patients at diagnosis, at re-evaluation or at time of medullary relapse. The study aim was to mention the correlation of CSF infiltration with clinical, laboratory and radiological findings in acute leukemia cases. The study is approved by the Institutional Review Board at the Mansoura University Hospital. Results: 53 cases included in the study. 2 cases were isolated CNS relapse without medullary relapse. CSF infiltration was found in 5 cases. CSF infiltration was significantly associated with Acute lymphoblastic leukemia (ALL) and LL parathesia and showed higher incidence among relapsed cases. Conclusion: Detailed physical examination including neurological examinations of acute leukemia patients is critical in driving the physician for possibility of CNS extension of the disease that has an impact on treatment plans. CSF examination is a cornerstone in investigational plans, especially in ALL patients