Background: CD47 is an immune‐regulatory protein that belongs to the immunoglobulin family. It inhibits the phagocytic ability of immune cells. So, it is related to an unfavorable outcome in leukemia and various solid tumors. One of the immune checkpoint molecules is cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) which interferes with anticancer immunity and has an important role in anti‐cancer surveillance. This study aimed to investigate CD47 and CTLA‐4 mRNA and protein expressions in relation to P53 mutation and different clinicopathological parameters in endometrial carcinoma (EC). We also investigated the relation between CD47 and CTLA‐4 expressions in EC. Subject & Method: This study included sixty‐eight patients with EC. Tissue samples of the tumor with adequate safety margin were obtained. Part of the tissues was preserved in formalin for histopathological and immunohistochemical examination while the other part was kept frozen at ‐80 °C for molecular profile. Results: CD47 and CTLA‐4 gene expressions were upregulated in the tissues of EC in comparison with the adjacent control tissues. Significantly higher CD47 and CTLA‐4 gene expressions were detected in the serous type, higher stage, muscle invasion ≥50 %, higher grade, LN metastasis, and distant metastasis. CD47 gene expression was a good marker of P53 mutation at a cut‐off of 1.65. It showed a high sensitivity of 84 %, a high specificity of 75.3 %, an average PPV of 65.6 %, a high NPV of 88.9 %, and an accuracy of 77.9 % (P < 0.001). Similarly, CTLA‐4 gene expression was a good marker of P53 mutation at a cut‐off of 3.75. It showed a sensitivity of 88 %, a specificity of 74.3 %, a PPV of 66.7 %, an NPV of 91.4 %, and an accuracy of 79.4 % (P < 0.001). Conclusion: CD47 and CTLA‐4 expressions can be considered possible diagnostic and prognostic markers in EC. They were good markers of P53 mutation, and higher tumor grades and stages