Fibronectin and CD44v6 are involved in tumor invasion and metastasis. We examined fibronectin and CD44v6 expression in normal liver and liver cancer by immunohistochemistry. Fibronectin expression was identified in 37.5% of liver cancer specimens. Well-differentiated tumors and expansive growth were associated with continuous periacinar, or cytoplasmic and periacinar fibronectin expression; poorly differentiated and invasive tumors showed interrupted periacinar or vascular mesenchymal fibronectin expression. CD44v6 expression was absent in controls but was observed in 67.5% of liver cancers. Increased CD44v6 expression was more common with poor clinical tumor characteristics. FN and CD44v6 are potential markers for determining liver cancer invasion and metastasis.