To compare the cytogenetic difference between M5a and M5b of acute monocytic leukemia and to study the correlation between karyotypes and clinical manifestations, a total of 58 cases of de novo adult AML M5 have been investigated. Chromosome metaphases of bone marrow cells were prepared by using direct method and 24 hours short-term culture. The karyotypes were analyzed by G-banding. Meanwhile, clinical information of these cases were studied retrospectively. The results showed that there were 28 with normal karyotype and 30 with aberrant karyotype in 58 cases. The frequency of normal karyotype in patients with M5b was significantly higher than that in patients with M5a (P = 0.0001). The 11q23 aberrations and trisomy 8 were more common in patients with M5a in comparison with patients with M5b (P < 0.01). The patients with AML M5 with aberrant karyotype had a higher incidence of hyperleukocytosis, extramedullary central nerve system infiltration, lower complete remission (CR) rate and shorter overall survival. It is concluded that acute monocytic leukemia is a series of heterogeneous diseases, a distinctive cytogenetic features can be observed between patients with AML M5a and M5b, these results will provide insights into the classification and pathogenesis mechanism of AML M5 at molecular level.