PURPOSE: Recent studies have shown a 7~15% lymph node (LN) metastasis rate in submucosal invasive colorectal cancer (SICC). Identification of risk factors for LN metastasis is crucial in the choice of therapeutic modalities for SICC. The present study was performed to assess the possibility of LN metastasis and to determine the risk factors of LN metastasis in SICC. METHODS: A retrospective study of 168 patients with SICC who underwent a curative resection between June 1989 and December 2004 at Asan Medical Center was conducted. The level of submucosal invasion was classified into upper third (sm1), middle third (sm2), and lower third (sm3) according to the submucosal depth of invasion. The following carcinoma-related variables were assessed: tumor size, tumor location, level of submucosal invasion, cell differentiation, lymphovascular invasion, neural invasion, and tumor cell dissociation (TCD). RESULTS: The overall LN metastasis rate was 14.3%. According to the level of submucosal invasion, LN metastasis was seen as follows: sm1, n=4 (4.2%), sm2, n= 10 (21.3%), and sm3, n=10 (38.5%) (P=0.039). According to cell differentiation, LN metastasis was observed as follows: well-differentiated, n=4 (4.9%), moderately differentiated, n=19 (22.9%), and poorly differentiated, n=1 (25.0%) (P=0.028). Nineteen of the 66 cases (28.8%) with TCD had significantly higher risk of LN metastasis as did 5 of the 102 cases (4.9%) without TCD (P=0.045). No statistical difference was observed in the risk of LN metastasis with regard to tumor location, tumor size, neural invasion, or lymphovascular invasion. CONCLUSIONS: Submucosal invasion, cell differentiation, and tumor cell dissociation were significant pathologic predictors of LN metastasis in SICC. As SICC has considerable risk of LN metastasis, local excision should be reserved to highly selective sm1 cancers.