Two hundred and four cytogenetically investigated patients with acute myeloid leukemia (AML) were evaluated for the presence (AR+) or absence (AR−) of Auer rods. Chromosome analysis was successful in 187 patients (92%). Seventy-eight patients (38%) were AR+. Cytogenetic abnormalities were detected in 35 (49%) AR+ patients and in 66 (57%) AR− patients. The proportion of patients with complex karyotypic changes (more than two aberrations) was significantly higher in the AR− group (p<0.01). Also, unidentifiable marker chromosomes were significantly more frequent in the AR− group (p<0.01). Twenty-one of 23 AR+, but none of 46 AR− patients with structural changes, had involvement of 21q22, 17q11–12, or 11p13–15. In contrast, structural changes of 1p, 5q, 7q, 9q, 11q, or 22q were present in 31 AR− but in only two AR+ patients. Four patients had translocations involving 21q22 without rearrangements of 8q22. All were AR+, but only one displayed M2 morphology. We draw the conclusion that chromosomal changes affecting 21q22 might be primarily related to AR formation, whereas, changes of 8q22 produce the characteristic differentiation pattern leading to M2 morphology, consistently found in AML with t(8;21)(q22;q22). With regard to numerical abnormalities, −7 and +8 occurred about equally often in the two groups, whereas, +11 and −Y, especially when present as the sole aberrations, were predominantly found in AR+ patients. In contrast, −5 and +21 were exclusively found in AR− patients. The results indicate that AR+ AML is characterized by a relatively limited number of chromosomal abnormalities that are different from the aberrations found in AR− patients. This feature has not been emphasized in previous studies correlating hematologic and cytogenetic findings in AML.