We investigated the relationship between the expression of epithelial cell adhesion molecule (EpCAM) and the occurrence and development of colon cancer. Fifty colon cancer tissues and adjacent normal tissues were collected, while 40 normal intestinal mucosa tissues were collected as the blank group. EpCAM expression was detected by immunohistochemistry and the patients were followed-up to evaluate the prognosis. The positive expression rate of EpCAM reached 93.7% in patients with colorectal carcinoma, which was significantly higher than that in the negative control group and blank group (14.8 and 12.7%, P < 0.05, respectively). There was no significant difference between the control group and blank group regarding EpCAM expression. No direct relationship was observed between EpCAM expression and patient age, gender, and other characteristics. EpCAM was overexpressed in colorectal cancer and had a high detection rate. EpCAM can be used as a diagnostic biomarker for clinical detection of colorectal cancer.