In patients with acute leukemia, aberrant expression of Cluster Differentiation (CD) markers may have an influence on clinical response, remission rate, and overall survival (OS). The current study aimed to evaluate the effect of aberrant expression of cluster differentiation markers on the prognosis of acute leukemia patients. The present cohort research included patients who were newly diagnosed with Acute Leukemia between January 2019 and December 2022 were included in the current cohort study. The current study comprised 163 individuals diagnosed with acute leukemia, including 98 patients with Acute Myeloid Leukemia (AML) (60.1%) and 65 patients with Acute Lymphoid Leukemia (ALL) (39.9%). The ratio of males to females was (1.1:1). According to the current study, 40.8% and 29.2% of AML and ALL patients showed aberrant expression, respectively. The current research also found that aberrant expression of CD2 in AML and CD13 in ALL was the most common. The current study's findings suggested that aberrant expressions CD2, CD5, and CD7 have been correlated with poor prognosis. However, no statistically significant differences were detected between the aberrant expressions of CD10, CD13, CD19, CD20, CD22, and CD33 markers and prognosis.