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Aim: The identification of cellular pathways in colorectal tumor biology is essential for early diagnosis, treatment, and post-treatment follow-up. Osteopontin is an extracellular matrix protein that has regulatory physiological functions and roles in apoptosis, proliferation, adhesion, invasion, and tumor metastasis. In this study, we aimed to determine the prognostic and predictive value of osteopontin in colon adenocarcinoma. Our study investigated whether osteopontin expression had any prognostic or predictive use in colon adenocarcinoma and also if there were any differences between adenocarcinoma and adenoma. Methods: Fifty of these colonic specimens were adenocarcinoma, 16 were adenomatous polyps, and 10 were nontumoral colonic tissue that served as a control group. We used a two-tiered evaluation system that examined both the staining intensity and the percentage of staining. Results: The staining scores of tumors with vascular invasion were significantly higher than those of tumors without vascular invasion (p=0.001). In addition, the tumoral tissues’ osteopontin staining scores were significantly higher than the score of polyps (p=0.001). Conclusion: If future studies support our results, we suggest that osteopontin may be an important biomarker for predicting or detecting vascular invasion in tumors and could be useful in tumor-adenomatous polyp differentiation. Therefore, osteopontin can provide helpful information in the diagnosis and prognosis of colon adenocarcinoma.