PurposeExtranodal extension (ENE) is closely associated with the aggressiveness of both colon and rectal cancer. This study evaluated the clinicopathologic significance and prognostic impact of ENE in separate populations of patients with colon and rectal cancers.Materials and MethodsThe medical records of 2,346 patients with colorectal cancer (CRC) who underwent curative surgery at our institution between January 2003 and December 2011 were clinically and histologically reviewed.ResultsENE was associated with younger age, advanced tumor stage, lymphovascular invasion (LVI), and perineural invasion (PNI) in both colon and rectal cancer. ENE rates differed significantly in patients with right colon (36.9%), left colon (42.6%), and rectal (48.7%) cancers (right vs. left, p=0.037; left vs. rectum, p=0.009). The 5-year disease-free survival (DFS) rate according to ENE status and primary tumor site differed significantly in patients with ENE-negative colon cancer (80.5%), ENE-negative rectal cancer (77.4%), ENE-positive colon cancer (68.6%), and ENE-positive rectal cancer (64.2%) (p<0.001). Multivariate analysis showed that advanced tumor stage, ENE, LVI, PNI, and absence of adjuvant chemotherapy were independently prognostic of reduced DFS in colon and rectal cancer patients.ConclusionENE is closely associated with the aggressiveness of colon and rectal cancers, with its frequency increasing from the right colon to the left colon to the rectum. ENE status is a significant independent predictor of DFS in CRC patients irrespective of tumor location. ENE might be more related with distally located CRC.