Background: Interval colon cancer occurs due to either limitations of colonoscopy or rapidly developing new tumors, possibly reflecting molecular and environmental differences in tumorigenesis. This study aimed to compare the clinicopathologic and molecular features of interval colon cancer with those of sporadic colon cancer in Asia. Methods: This prospective, multicenter, cross‐sectional study was conducted from May 2017 to December 2021 at six university hospitals in South Korea. Interval colon cancer was defined as colon cancer diagnosed within 5 years of complete colonoscopy. We compared the clinicopathologic and molecular biological characteristics, including CpG island methylator phenotype (CIMP), KRAS, BRAF, and microsatellite instability (MSI), between patients with interval and sporadic colon cancers. Results: We compared and analyzed 28 patients with interval colon cancer and 72 patients with sporadic cancer. There was no difference in terms of sex, BMI, underlying disease, and family history in the clinical comparison between the interval and sporadic cancer groups. There was no difference in the location, shape, or stage of cancer including metastasis, between the two groups. In molecular biological analysis, CIMP was 5.1% positive for sporadic cancer and 17.9% positive for interval colon cancer, indicating an approximately 13% greater frequency in interval colon cancer (p = .036). KRAR mutation was observed in 36.7% of patients with sporadic cancers and 17.9% of those with interval colon, which was about 18% higher in sporadic cancer, but there was no statistically significant difference (p = .066). There was no difference between MSI and BRAF genotype between the sporadic and interval cancer groups. Conclusions: Unlike the findings of western studies, there was no clinical difference between sporadic and interval colon cancer. In molecular biological comparison, the CIMP positivity rate was significantly higher in patients with interval colon cancer.