Background: Endometrial carcinoma (EC) is the most common gynecologic tumor in the developed world and ranks second in Egypt. Ribosome-binding protein 1 (RRBP1) is a membrane protein of rough endoplasmic reticulum essential for stabilization of endoplasmic reticulum. Overexpression of RRBP1 was detected in several malignant tumors. p53 is a tumor suppressor transcription factor encoded by TP53. The mutation of TP53 is considered the most common significant molecular alteration in half of human cancers. Aim: This study aimed to explore the immunohistochemical expression of RRBP1 in wild and mutated p53 immunophenotype endometrioid EC in relation to estrogen receptor alpha (ER-α) status and clinicopathological factors. Materials and Methods: Fifty-six endometrioid EC paraffin blocks were collected. Sections were stained with anti-RRBP1, anti-p53, and anti-ER-α antibodies. Results: RRBP1 overexpression was significantly related to high tumor grade, presence of lymphovascular invasion (LVI), advanced TNM staging, and negative ER-α. Mutated-type p53 expression was associated with high grade, LVI, advanced TNM staging, and negative ER-α. A Significant difference in p53 expression patterns was detected in relation to clinicopathological prognostic factors. Studied tumors with positive ER-α nuclear expression significantly showed wild-type p53 expression patterns more frequently compared to EEC with negative ER-α expression. Furthermore, a positive correlation was detected between RRBP1 overexpression and mutated-type p53. Conclusion: RRBP1 is considered a bad prognostic indicator in EEC and together with mutated p53 expression could be beneficial as a potential therapeutic target for EC.