We present unique chromosomal abnormalities found in a patient with acute myeloblastic leukemia (AML) of French-American-British subtype M2. The patient was referred for an evaluation of chromosomal anomaly associated with AML. She was found to have an abnormal karyotype 46,XX,t(8;21)(q22;q22), and a questionable dup(15)(q15q22) in the majority of cells analyzed. Two cells had the same chromosomal anomalies plus a duplicated derivative chromosome 21 [der(21)t(8;21)(q22;q22)]. These cytogenetic findings were confirmed by fluorescence in situ hybridization utilizing the appropriate DNA probes. To our knowledge, this is the first case report of a combination of the translocation between chromosomes 8 and 21, a duplication of chromosome 15 [dup(15)(q15q22), and a duplicated derivative chromosome 21 [der(21)t(8;21)(q22;q22)].