Matrix metalloproteinase-2 (MMP-2) and cathepsin D (CD) play a significant role in degrading the components of basement membrane and extracellular matrix (ECM), whereas tenascin-C (TN-C) is a glycoprotein of the ECM related to cell adhesion and detachment. These proteins have been implicated in tumor invasion and metastasis. Therefore, we aimed at investigating the prognostic significance of MMP-2, CD, and TN-C expressions in primary colorectal cancer. Overall, 112 colorectal adenocarcinomas were included in the present study. MMP-2, CD, and TN-C expressions were evaluated by immunohistochemistry and correlated with clinicopathologic prognostic parameters and survival. Diffuse stromal TN-C immunostaining was found to be significantly correlated with advanced stage and shorter survival time (p = 0.002 and 0.02, respectively). MMP-2 expression was found to correlate with lymph vessel invasion (p = 0.006) and stage (p = 0.03). CD expression was related to depth of invasion (p = 0.005). No significant relationship was found between survival and MMP-2 and CD expression (p > 0.05). In multivariate analysis, stage and vascular invasion were independent prognostic factors, whereas TN-C did not retain a clear independent relationship to survival (p > 0.05). Our findings suggest that TN-C expression may be a potential prognostic marker in colorectal carcinoma. However, MMP-2 and CD do not appear to be significant indicators of survival.