Background: CLL is an adult leukemia presented with a clonal accumulation of lymphocytes. Immunophenotypic changes can be effective in predicting clinical course, the survival of patients, and determining first-line treatment. Methodology: The current research used lymphoma data obtained from El-Obeid Oncology Center. Included were details pertaining to lymphoma patients who received their diagnoses between January 2018 and January 2020. One hundred patients, including sixty-one with CLL and forty-nine without, made up the full coverage sample. Immunohistochemistry and molecular analyses were conducted on a subset of individuals. Additionally, several patients underwent flow cytometry analysis for some CD markers as well as microRNA prediction. Results: CD19 was shown to be positively expressed in all CLL patients studied (100%), while 88% of non-CLL patients also showed the same expression. Ninety-three percent of the CLL patients and nine percent of the non-CLL patients examined showed CD5-positive expressions. Only 16.7% of CLL patients and 66.7% of non-CLL patients tested positive for CD22. Among the CLL patients studied, 92.3% showed CD23 positive expressions, while no non-CLL patients did. Every single patient with CLL and every single patient without CLL tested negative for CD38. We observed the presence of FMC70 in 16.7% of the analyzed CLL samples and in two out of the three non-CLL cases. We evaluated the predictive significance of microRNA in a cohort of 12 patients, finding that around 83% showed positive expression. Conclusion: CLL is more prevalent in Sudan than the reported global epidemiology and more common among elder men than non-CLL variants. According to the molecular prognostic markers, CLL has bad prognostic indicators.