Background: Patients with lymph node metastasis of colorectal cancer (CRC) have a greater risk of recurrence. However, the characteristics of benign mesenteric lymph node enlargement (BLNE) are not well documented. The aim of this study is to assess clinical and prognostic significance of BLNE in patients with CRC. Methods: 601 patients who underwent surgery for stage 0, I, II CRC from January 2010 to April 2014 were included and separated into two groups by presence of BLNE. Univariate and multivariate analyses were constructed to demonstrate prognostic factors between BLNE group (n = 275) and control group (n = 326). Results: The risk of recurrence in BLNE group after curative resection was significantly lower than control group, with the 1-, 3-, and 5-year disease-free survival rates being 98.2, 91.6, and 86.9 %, in BLNE group and 95.7, 86.2, and 78.2 %, in control group respectively (p = 0.004). The mortality in BLNE group was lower compared with non BLNE group (mean overall survival: 95.7±1.2 vs. 89.5±1.4 months, p = 0.001). Patients of BLNE group also had a higher percentage of younger age, family tumor history, left sided tumors and tumor size ≥4cm. Adjusted Cox regression showed BLNE was an independent prognostic factor for both disease free survival and overall survival (P= 0.003 and 0.001). Conclusions: The study indicates that BLNE can be a useful positive factor in predicting recurrence and long-term survival concerning CRC patients. This conclusion offers a new viewpoint about CRC genesis and progression.