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Ataxia–telangiectasia mutated (<i>ATM</i>) is a key DNA damage signaling kinase that is mutated in humans with ataxia–telangiectasia (A-T) syndrome. This syndrome is characterized by neurodegeneration, immune abnormality, cancer predisposition, and premature aging. To better understand the function of <i>ATM</i> in vivo, we engineered a viable zebrafish model with a mutated <i>atm</i> gene. Zebrafish <i>atm</i> loss-of-function mutants show characteristic features of A-T-like motor disturbance, including coordination disorders, immunodeficiency, and tumorigenesis. The immunological disorder of <i>atm</i> homozygote fish is linked to the developmental blockade of hematopoiesis, which occurs at the adulthood stage and results in a decrease in infection defense but, with little effect on wound healing. Malignant neoplasms found in <i>atm</i> mutant fish were mainly nerve sheath tumors and myeloid leukemia, which rarely occur in A-T patients or <i>Atm−/−</i> mice. These results underscore the importance of <i>atm</i> during immune cell development. This zebrafish A-T model opens up a pathway to an improved understanding of the molecular basis of tumorigenesis in A-T and the cellular role of <i>atm</i>.