Ataxia telangiectasia (A-T) is a rare childhood autosomal recessive neurodegenerative chromosomal instability disorder. It is characterized by high risk of hematological malignancies with T-cell phenotype being the most common, which can present first before the diagnosis of A-T made. The chromosomal instability in A-T increases the toxicity to radio- chemotherapeutic agents, creating the treatment modification challenges and the deviation from the optimal management protocols. In this case report we present a 14-month-old boy diagnosed as T cell –ALL. Based on his early presentation, family history of childhood lymphoma, and high AFP, inherited predisposition was suspected, and genetic testing confirm A-T. This report represents the crucial part of clinical suspicion of A-T in similar cases as well as highlighting the importance of an early A-T diagnosis that prevents toxic death due to the extensive regimen of radio- chemotherapeutic agents. The report summarizes the toxicity and modification challenges during management with literature review for the chemotherapy modification experience in such cases.