This study was aimed to investigate the clinical features of CD56(+) patients with acute monocytic leukemia (AML-M5) and their prognostic significance. The data of 76 newly-diagnosed patients from our hospital were analyzed retrospectively. Patients were divided into two groups: CD56(+) group (21 patients) and CD56(-) group (55 patients). The clinical features, CR rate, relapse rate, the duration of CR, and survival time of patients between the two groups were compared. The results indicated that the CD56(+) antigen was observed in 21 patients (27.6%), their median age was 51.5 years and with a range 16 - 70 years. Of the 21 CD56(+) patients, the high WBC count was found in 57.1% CD56(+) patients (12/21), but it only in 15% CD56(-) patients (P < 0.05). The extramedullary infiltration was seen in 13 CD56(+) patients, and accounted for 62% (13/21), meanwhile this infiltration was found in 18 CD56(-) patients (18/55) and accounted for 33% (P < 0.05). All cases immunophenotypically highly expressed CD13, CD33, CD64, CD11b, cMPO, CD38, in which only the expression frequency of CD11b was positively related with CD56 (r = 0.59, P < 0.05). The CR rate in CD56(+) group accounted for 60.0%, and had no significant difference in comparison with that in CD56(-) group. In CD56(+) group the relapse rate was 75% (P = 0.042), the mean duration of CR was 5.5 months (95%CI, 3.1 - 8.6, P = 0.002), the median overall survival time was 10.1 months (95%CI, 2.3 - 16.3, P = 0.001). and all these had statistical significance as compared with that in CD56(-) group. It is concluded that CD56(+) AML-M5 patients always complicate with high WBC count and extramedullary infiltration, their CR rate and duration of CR are lower and shorter respectively, their relapse rate and prognosis are high and poor respectively.