We describe a case of acute myeloid leukemia (AML) in which trisomy 21 was the sole acquired cytogenetic abnormality. The immunophenotype showed positivity for CD7 and CD9 along with CD13, CD33, and CD34. The chromosomal analysis of bone marrow showed 47,XY +21 in all the metaphases analyzed. The constitutional karyotype was normal. The patient was an adult and did not have any features of Down's syndrome. The bone marrow morphology was AML-M2 as per the French-American-British (FAB) criteria. A final diagnosis of CD7- and CD9-positive AML-M2 was established with trisomy 21 as a sole cytogenetic abnormality. The patient responded remarkably well to chemotherapy and achieved complete clinical remission. This is the first case of CD7- and CD9-positive AML with trisomy 21 as a sole abnormality. A putative role for the co-expression of abnormal lymphoid markers in achieving quick remission is discussed.