Background: CXCR4 and RKIP have been implicated in tumorigenesis and progression in many cancers, but their significance in gastric carcinoma remains unclear. Aim: The aim of this study is to assess their possible significance in gastric carcinoma and premalignant lesions of the stomach. Methods: This retrospective study was carried upon 50 cases of gastric adenocarcinoma and twenty cases from premalignant lesions. Immunohistochemistry was performed to examine the expression of CXCR4 and RKIP in both gastric adenocarcinoma and premalignant lesions. Results: CXCR4 was found highly expressed in gastric carcinoma. It was significantly correlated with tumor grade, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage. RKIP was negatively correlated with advanced tumor grade, depth of tumor invasion, distant metastasis and TNM stage. No significant correlation between CXCR4 and RKIP expression in studied cases was detected. Conclusions: The results suggested that both CXCR4 and RKIP might be involved in gastric carcinogenesis. Therefore, Both CXCR4 and RKIP could be considered as prognostic markers in gastric carcinoma.