Introduction: Acute lymphoblastic leukemia
(ALL) had common clinical presentation associated with bone marrow infiltration by leukemic
cells. Rarely can it be presented with unusual signs related to extramedullary involvement that may be lead to delay diagnosis of ALL in children. Method: The following databases including PubMed, EMBASE, Science Direct and Google Scholar were searched for all relevant subjects from April 1986 to April 2016. To search for review articles, following terms alone or in combination were used: “Acute Lymphoblastic Leukemia
”, “Unusual Presentation”, “Childhood Leukemia
”, “Rare Presentation” and “Atypical Presentation”. Inclusion criteria for this review study were all case reported study about unusual clinical presentations of acute lymphoblastic leukemia
in pediatrics. Results: Of the total number of 56 studies, 41 had inclusion criteria. In this review study, the most common unusual initial presentation of ALL in children was related to musculoskeletal symptoms (34.2%) especially bony symptoms ( bone pain,
multiple bone fractures, osteoporosis, multifocal osteomyelitis and calf pain) and hypercalcemia. The other unusual initial presentations of ALL in order of frequency include renal involvement (14.6%), neurologic signs (14.6%), orbital manifestations (12.2%), pericardial involvement (4.9%) and other rare miscellaneous presentations (19.5%). Conclusion: The clinician must be familiar with these unusual presentations of ALL in pediatrics in order to avoid delay diagnosis of this disease and increase survival by early detection.