Background: Since epithelial cell adhesion molecule glycoprotein (EPCAM) is associated with the development and metastasis of colon adenocarcinoma, it can be helpful in predicting the tumor stage before surgery. In this study, we investigated EPCAM glycoprotein expression in colon adenocarcinoma and its relationship with tumor staging. Materials and Methods: This study was done on formalin-fixed and paraffin-embedded tissues of 71 patients diagnosed with colon adenocarcinoma, together with normal tissues around them, which were available at the archive of pathology lab of Al-Zahra hospital, Isfahan. Hematoxylin and eosin (HandE) and immunohistochemistry (IHC) staining methods for EPCAM marker were performed on paraffin-embedded blocks. Results: The percentage of staining of EPCAM glycoprotein in the tumoral and normal tissues of 71 patients with colon adenocarcinoma was studied and compared. In normal tissue, 84.5% showed strong staining, 15.5% showed moderate to strong, and none of the patients showed moderate, weak, or no staining at all. In the tumoral tissue, 25.4% had strong, 25.4% had moderate to strong, 26.8% showed moderate, 16.9% showed weak and 5.6% had no staining at all. EPCAM expression was significantly less in tumoral tissue than in normal. Conclusion: There was an inverse relationship between tumor staging and the percentage of staining in EPCAM glycoprotein so this marker can be used for predicting the tumor stage.