Abstract: Objective: To explore the distribution of tumor budding and the expression of osteopontin in primary colorectal cancer and tumor buds in order to evaluate whether these factors could be used as a simple biological indicator for predicting liver metastasis after surgery to remove colorectal carcinoma. Methods: Cases diagnosed as Duke's stage C were divided into three groups, namely, group A with synchronous liver metastasis, group B with heterochronous liver metastasis, and group C with no liver metastasis. After H&E staining, attention was focused on observing the distribution characteristics of tumor budding at the invasive front of colorectal carcinoma and recording the numbers accurately.The expression of osteopontin and NF- κ B in primary lesions and tumor buds was examined using im-munohistochemistry. Results: Tumor budding was defined as depolarized and dedifferentiated cancer cells with isolated and irregular trabecular form ahead of the invasive front of the lesion. Both the degree of tumor budding and the strong positive expression of osteopontin in primary colorectal cancer showed a significant difference only between group A and group B (P<0.01). The positive expression of osteopontin in tumor buds showed a significant difference between groups A and C and between groups B and C (P<0.01). As for the expression of NF- κ B, there is no significant difference among the 3 groups. Conclusion: Both tumor budding degree (BD)(+) and the strong positive expression of osteopon-tin in primary colorectal cancer indicate increased risk of liver metastasis following colorectal carcinoma. If the distribution characteristics of tumor budding are assessed in combination with the expression of osteopontin within the tumor buds, the predictive accuracy is increased and can be used as a biological indicator for predicting liver metastasis after surgery to remove colorectal carcinoma.