Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is the most common hematological malignancy in children, and the t(12;21)(p13;q22) occurs in approximately 25% of these cases, making it is the most prevalent chromosomal abnormality. The t(12;21) which disrupts hematopoietic differentiation and proliferation, and can be present as a sole abnormality or within the context of a complex karyotype characterized by three or more chromosomal abnormalities. The prognosis of t(12;21) within a complex karyotype is extensively debated. In this review, we discuss the literature regarding t(12;21) and summarize the cytogenetic features found in 363 pediatric cases compiled from the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer. Cytogenetically, most of the cases had secondary chromosomal abnormalities, about half of which were in the context of a complex karyotype. Trisomy 21 was found to be the most common numerical abnormality in almost one-fifth of the cases, and deletions on chromosome 12 and 6 occurred in 16.9% and 12.5% of cases, respectively. In general, t(12;21) in B-ALL is associated with a favorable prognosis. Herein, we found no significant difference in survival outcome of t(12;21) with a on-complex or complex karyotype.