Epithelial cell transforming 2 (Ect2) protein is a member of the human diffuse B-cell lymphoma family of guanine nucleotide exchange factors, which activate the Ras homolog gene family of small GTPases; however, the clinical implications of Ect2 in colorectal carcinoma (CRC) are unclear. The present study aimed to determine the relationship between Ect2 expression and prognosis in patients with CRC. Western blot analysis and immunohistochemistry assays were used to determine the expression of Ect2 in CRC and paired non-cancerous tissues from 66 patients. The correlation between Ect2 expression and clinicopathological parameters was assessed using χ2 tests. Patient survival was determined using the Kaplan-Meier method and log-rank test. Cox regression was used for multivariate analysis of prognostic factors. Results demonstrated that Ect2 protein was highly expressed in human CRC samples [29/45 (64.45%)] and significantly correlated with a poor prognosis (P<0.05). Compared with normal tissues, CRC tissues demonstrated higher expression levels of Ect2 mRNA [44/66 (66.67%)]. In addition, highly-expressed Ect2 was significantly associated with recurrence (P=0.023) and invasion (P=0.008) of CRC. High Ect2 expression levels in patients were associated with poorer overall survival (OS) and disease-free survival (DFS) compared with lower expression levels of Ect2. Based on multivariate analysis, Ect2 overexpression was significantly correlated with OS and DFS (P=0.015 and 0.020, respectively). In conclusion, Ect2 overexpression is an independent and important prognostic factor for OS and DFS in patients with CRC.