This study aimed to identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, and therapeutic outcome. MicroRNA microarray profiling was performed on 84 patients with incident colon adenocarcinoma, and the associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy were evaluated. Thirty-seven microRNAs were differentially expressed in tumors, and five (miR-20a, miR-21, miR-106a, miR-181b, and miR-203) were validated in an independent Chinese cohort of 113 patients. Higher miR-21 expression was associated with poor survival and therapeutic outcome in both cohorts, independent of clinical covariates. In situ hybridization demonstrated high miR-21 expression in colonic carcinoma cells. These findings suggest that miR-21 may be a useful diagnostic biomarker and prognostic indicator for colon adenocarcinomas.This study aimed to identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, and therapeutic outcome. MicroRNA microarray profiling was performed on 84 patients with incident colon adenocarcinoma, and the associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy were evaluated. Thirty-seven microRNAs were differentially expressed in tumors, and five (miR-20a, miR-21, miR-106a, miR-181b, and miR-203) were validated in an independent Chinese cohort of 113 patients. Higher miR-21 expression was associated with poor survival and therapeutic outcome in both cohorts, independent of clinical covariates. In situ hybridization demonstrated high miR-21 expression in colonic carcinoma cells. These findings suggest that miR-21 may be a useful diagnostic biomarker and prognostic indicator for colon adenocarcinomas.