INTRODUCTION: Benign lymph node enlargement (BLNE) is common in colorectal cancer; however, few studies have investigated its influence on prognosis, clinicopathological features, and pathogenesis. METHODS: A cohort study was conducted to analyze the clinicopathologic features and prognosis of colorectal cancer patients, categorized based on the presence or absence of BLNE. Given the correlation between lymph nodes and immune response, immunohistochemistry, transcriptome analysis, and exon sequencing were employed to further investigate the differences in the immune microenvironment of primary tumors. RESULTS: Overall, 630 AJCC stage I/II patients were included in the study, with 131 in the BLNE group and 499 in the Non-BLNE (NBLNE) group. Patients in the BLNE group were found to have a significantly better disease-free survival (DFS) (hazard ratio [HR] 0.44, P = 0.016) and overall survival (OS) (HR 0.46, P = 0.011) than those in the NBLNE group. Pathologically, compared with the NBLNE group, the BLNE group had more mature tertiary lymphoid structures (66.7 % vs. 36.5 %, P = 0.002) and higher immunoscores (18.8 % vs. 2.1 %, P = 0.004) in primary tumor tissue. Also, transcriptome analysis showed that, compared with NBLNE, the genes upregulated in BLNE were enriched in immune-related pathways, such as adaptive immune response and immuno-regulatory interactions. Whole-exon sequencing analysis revealed a higher tumor mutation burden (TMB) in the BLNE group [6.03 (5.59, 7.59) vs. 5.33 (4.62, 6.34), P = 0.025]. CONCLUSION: BLNE is positively associated with the prognosis of colorectal cancer, possibly because patients with BLNE have a stronger anti-tumor immune response.