This study was aimed to investigate the expression of CD96 on bone marrow mononuclear cells (BMMNC) from 91 patients with acute leukemia, and the results were analyzed with clinical pathological data. Flow cytometry was used to detect CD96 molecule on the bone marrow mononuclear cell surface of 91 newly diagnosed patients with acute leukemia, and 15 healthy adults were served as normal controls. The results showed that the average rate of CD96(+) expression on BMMNC (CD45(+) CD34(+) CD19(+)) of 21 patients with B-ALL was (17.41 ± 27.97)%, the average rate of CD96(+) expression on stem cells (CD45(+)CD34(+)CD7(+)) of 11 patients with T-ALL was (46.98 ± 45.55)%, the average rate of CD96(+) expression on BMMNC (CD45(+)CD34(+)CD38(-)) of 59 patients with AML was (16.69 ± 25.08)%, while the average rate of CD96(+) on BMMNC of healthy adult controls was (0.52 ± 1.84)%, there was significant difference in average rate of CD96(+) expression between above-mentioned patients and healthy adult controls (p 0.05). The leukocyte count, hemoglobin level and platelet count in CD96(+) group had no obvious difference from CD96(-) ones (p > 0.05). No change found in the field of molecular biology and cytogenetic between these 2 groups. It is concluded that CD96 expression is different in different types of leukemia. The positive expression of CD96 on bone marrow hematopoietic stem cells in patients with acute leukemia may be associated with primary drug resistance, relapse and progression. The CD96 on BMMNC of acute leukemias can be a helpful prognostic indicator in treatment response assessment.