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Background: Acute lymphoblastic leukemia (ALL) is one of the blood cancers responsible for 80% of children's leukemia and is also the most common malignancy in patients aged under 14 years (frequency of 23% among all types of cancers). Regarding the importance of identifying clinical symptoms to diagnose the disease in the early stages, this study is conducted to investigate the symptoms at diagnosis in ALL children. Methods: In this retrospective cohort study, 350 patients aged under 14, referring to four hospitals of Shiraz University of Medical Sciences as reference hospitals in Southern Iran, participated between 2013 and 2019. Their information was collected using patients' records, and the data were analyzed using SPSS version16. Results: Based on the findings of this study, the first clinical manifestations of the disease happened suddenly and acute, occurring within a few days to a maximum of 6 weeks before diagnosis. Fever (70%) and hepatomegaly (60%) were the most common signs and symptoms in patients. However, a significant percentage of ALL patients referred with non-specific symptoms. Conclusion: The results of this study indicate the importance of recognizing common and unusual signs and symptoms based on a complete and thorough history taking and accurate physical examination as well as rare symptoms that may be ignored or misdiagnosed by physicians. The knowledge of common signs and symptoms results in early diagnosis of the disease in early stages. [ABSTRACT FROM AUTHOR]