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Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) has been recently identified as a marker of aggressive behavior in several types of tumors. The aim of the present study was to detect the expression of the IMP3 protein in colorectal adenocarcinoma (CRA) and to identify a correlation with the clinicopathological features of the disease. IMP3 was evaluated in 186 samples of CRA using immunohistochemical methods. The correlation between IMP3 expression and the clinicopathological features of colorectal cancer was evaluated by the χ2 and Fisher’s exact tests. Survival rates were calculated using the Kaplan-Meier method and the correlation between IMP3 protein expression and the prognosis of patients with CRA was analyzed using Cox analysis. Of the 186 adjacent normal mucosa (ANM) cases, the 22 that exhibited dysplasia demonstrated weak IMP3 expression and the 164 without dysplasia showed no expression. Of the 186 CRA cases, immunohistochemical staining for IMP3 was observed in 143 cases (76.9%). A comparison of IMP3 expression between the CRA and ANM samples revealed stronger immunohistochemical reactivity in the CRA tissues (P<0.01). High IMP3 expression was associated with differentiation, lymphoid metastasis, TNM stage, Ki-67 labeling index and a poor patient outcome (P<0.05). In the multivariate analysis, IMP3 emerged as an independent predictor of survival. The present study demonstrated that IMP3 is able to promote the aggressiveness of cancer behavior, resulting in a poor prognosis for patients with CRA. Consequently, IMP3 may be regarded as a novel proliferation and prognostic indicator for patients with CRA.