Background: Colorectal cancer is considered the third most prevalent cancer in both sexes. Immune checkpoint receptors that regulate T-cell response, stimulation, and development include lymphocyte activating gene 3 (LAG-3), cytotoxic T lymphocyte associated antigen-4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (Tim-3). In addition, they are crucial for the advancement of cancer and tumor immune escape. Objective: This work’s aim was to assess the immunohisto chemistry expression of Tim-3, CTLA-4, and LAG-3 in cancer cells and tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) and the correlation between these markers and clinicopathological variables and survival data. Methods: This study involved 206 CRC specimens processed for CTLA-4, LAG3, and TIM-3 immunohistochemistry and corre lated with the clinicopathological and survival parameters of the patients. Results: High CTLA-4 epithelial expression was highly related to the old age group, large tumor size, low tumor-stroma ratio (TSR), high grade, advanced stage, the presence of distant metastasis (DM), perineural invasion (PNI), necrosis, lympho vascular invasion (LVI), relapse, mortality, overall survival (OS), and disease-free survival (DFS), while negative CTLA-4 TILs expression was highly linked with the presence of gross perfo ration, low TSR, high tumor budding (TB) score, high grade, advanced stage, the existence of lymph node (LN) metastasis,