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Introduction: A prototype of good prognosis, t(8;21)‐positive AML, has diverse clinical and genetic features which affect its outcome. This study aimed at evaluating the clinico‐pathological spectrum of t(8;21)‐positive AML and ascertaining prognostic factors influencing its outcome in the Indian subcontinent. Methods: A retrospective analysis of 75 cases of t(8;21)‐positive AML diagnosed over a period of six years (2013‐2018) was carried out. Detailed clinical and laboratory data of the patients were collected from the electronic medical records and reviewed. Results: Median age was 19.5 years (range 5‐75 years) with a M:F of 1.7. Myeloid sarcoma was observed in 9.3% cases. There were 85% FAB AML‐M2, 8% AML‐M1, and 7% AML‐M4 subtypes. Prominent morphological characteristics included dyspoiesis in maturing myeloid cells (83%), long thin tapered Auer rods (58%), cytoplasmic vacuoles (58%), eosinophilia (50%), and mast cells (22%). Auer rods in maturing granulocytes (4% cases) were highly suggestive of the translocation. Additional cytogenetic abnormalities were present in 53% cases. Seventy‐one percent (25/35) achieved CR. The overall survival (OS) was 40%, with a median follow‐up of 27 months (range 4‐57 months). None of the hematological or cytogenetic factors correlated with OS, except for the presence of myeloid sarcoma which had a trend toward poor survival (P =.07). Conclusion: Outcome of t(8;21) AML is not influenced by any of the clinico‐pathological parameters, except for a myeloid sarcoma, which may herald a poor prognosis. Recognition of this distinct subtype of AML would facilitate further molecular screening for risk stratification in resource‐constrained settings. [ABSTRACT FROM AUTHOR]