Background: Acute myeloid leukemia (AML) is a heterogeneous group of malignant neoplasm of hematopoietic disorders characterized by an abnormal proliferation of myeloid precursors. Variant forms of classic translocation t(8;21) are uncommon, and either third or fourth chromosomes accounts for approximately 3-4% in acute myeloid leukemia. Case Report: We report a rare case of a 16-year old male having t(8;19;21)(q22;q13;q22) associated with  loss of sex chromosome. To the best of our knowledge, only few cases are described with variants of t(8;21) in AML and we first time report the involvement of 19q13 breakpoint region in AML. Conclusion: Translocation t(8;19;21)(q22;q13;q22) is a novel, rare but recurrent variant translocation of t(8;21). Due to the rarity of this translocation future accumulation of similar cases needed to evaluate clinical as well as prognostic and biological features.