The study aimed to assess the expression of CD49d and CD26 in newly diagnosed CLL patients and find their correlation with clinical Binet stage, and other clinical parameters. This study was conducted on 51 newly diagnosed CLL patients based on lymphocyte count > 5×109/L and immunophenotyping. The expression of CD49d, and CD26 were investigated using eight-color flow cytometer. The expression of CD49d and CD26 were detected in 56.9 %, 68.8 % of CLL patients, respectively. The correlation between CD49d expression and CD26 expression was statistically significant (p < 0.001) with high concordance rate between them. The positive expression of both CD49d and CD26 had statistically significant association with clinical Binet staging (p < 0.001, and 0.001, respectively) and their combined positive expression had also statistically significant association with clinical Binet stage of the disease (p < 0.001) with the highest combined positive rate was associated with stage C then followed by B in comparison with stage A. Conclusion: Positive CD49d and CD26 expressions were significantly correlated with advanced clinical Binet stage and associated with frequent lymphadenopathy and their combined positive expression had highly significant correlation with advanced clinical Binet stage and therefore their co expression could be beneficial as reliable prognostic indicator in CLL patients.