Background:Worldwide, gastric carcinoma (GC) is the 5th most common malignancies in both sexes representing 6.8% of thetotal fatalities and is the 3rd leading cause of cancer death representing 8.8% of total fatalities. In Egypt, GC considers the 12thleading cause of cancer death representing 2.2% of the total cancer mortality. A growing body of evidence supports that cancer stem cells (CSCs) are resistant to chemotherapy or radiation, and the cell adhesion molecule CD44 has been identified as a cell surface marker associated with cancer stem cell in several types of tumors including gastric cancer. CD44 regulates gastric stem cell proliferation by increasing cyclin D1 expression which represents an important regulatory protein in the cell cycle transition from G1 phase to S phase. This study aimed to investigate whether cyclin D1 and CD44 can be used as prognostic indicators in gastric cancer. Purpose :The study aimed to investigate whether cyclin D1 and CD44 can be used as prognostic indicators in gastric cancer. Material and Methods Forty formalin-fixed and paraffin-embedded gastric tissues, obtained from patients who underwentendoscopic resection or surgical resection, constituted the group of our study. The immunohistochemical expression of cyclin D1 and CD44 was examined and correlated with clinical-pathological parameters and outcome of the patients. Results: Overexpression of CD44 and cyclin D1 was noted (in of 55 and 50% respectively). Cyclin D1 and CD44 positive expressions in GC were positively correlated with tumor differentiation (p = 0.020, p = 0.004 respectively), TNM stage (p < 0.001 for both), poor survival (p < 0.001 for both), and with increased rate of recurrence (p = 0.020, p = 0.005 respectively). Conclusion :CD44 and cyclin D1 were associated with poor prognosis in gastric cancer, and so, they comprise an attractive target for anticancer drug development.