Introduction Translocation t(12;21)(p13;q22), a recurrent and an invisible chromosomal abnormality, resulting in TEL/AML1 gene fusion, associated with good prognosis, has been described to be a common abnormality, in children with B-acute lymphoblastic leukemia (B-ALL). Objectives The initial observation of very few TEL/AML1 positive patients at this center on testing by fluorescence in situ hybridization (FISH) led to study the prevalence of the abnormality, compare with the global distribution, and evaluate clinical, pathological, molecular, and cytogenetic features in TEL/AML1 positive patients. Materials and Methods A retrospective study of all B-ALL patients tested for TEL/AML1 gene fusion during the period January 2009 to November 2020 was undertaken. Clinicopathological, molecular, cytogenetic, treatment, and follow-up details were collected. All publications dealing with TEL/AML1 gene rearrangement were reviewed post Google and PubMed search. Results TEL/AML1gene rearrangement was assessed by FISH in 178 patients and by reverse transcription polymerase chain reaction in 36 patients and detected as the sole abnormality in 8.4% patients with additional genetic abnormalities noted on FISH evaluation. Normal karyotype was noted in 14/18 (77.7%) of these patients and 2 had complex karyotype. Complete blood count revealed hemoglobin to range from 35 to 116 g/L (median: 74 g/L), white blood count: 1.01–110×109/L (median: 7.8×109/L), platelet counts: 10–115×109/L (median: 42×109/L), blast count in peripheral smear: 0–98% (median: 41%). Immunophenotyping demonstrated 94.4% were CD34 positive, common acute lymphoblastic leukemia associated antigen (CALLA) positive with aberrant expression of CD13, CD33, CD56, singly or in combination in 58.8%. Conclusion TEL/AML1 fusion is rare in Indian patients with B-ALL and appears to be much rarer in our region. The detection of relevant specific abnormalities is of fundamental importance in B-ALL patients and these geographic variations can be used in defining management policies.