The diagnosis and prognosis of acute myeloid leukemia (AML) are closely related to cytogenetic and molecular biological abnormalities in patients. t (X; 21) (p11; q22), as a novel rare recurrent genetic abnormality, has previously been reported in adult AML patients; it is predominant in males, is advanced in age, and is associated with shorter survival. Here, we report a female pediatric AML patient who carried translocations of Xp11 and 21q22 bands. The translocation was not isolated but incorporated trisomy 8. By second-generation sequencing, the translocation was also accompanied by a relatively rare myeloid-related gene, CBL gene mutation. The patient responded well to conventional intensive chemotherapy and achieved remission during the first induction, but remission was maintained for only 9 months, and the patient subsequently died due to leukemia relapse. To our knowledge, this is the first report of t(X; 21) (p11; q22) in pediatric AML patients, which may be associated with a poor prognosis, underscoring the need for additional treatment options to improve outcomes.