Objective. The chemokine receptor CXCR4 and its ligand CXCL12 have been suggested to play important roles in the initiation or progression of cancers. The goal of the present study was to investigate alterations of CXCL12/CXCR4 in oral premalignant lesions and oral squamous cell carcinoma (OSCC). Methods. In 13 normal oral epithelia, 24 dysplastic oral leukoplakia (OLK), and 40 OSCC specimens, expressions of CXCL12 and CXCR4 were evaluated by immunohistochemistry. Results. CXCR4 was expressed in 37.5% of OLK and 60% of OSCC. CXCL12 was detected in 50% of OLK and 62.5% of OSCC. In OLK, CXCR4 positive ratio showed no significant difference from normal epithelia, but the CXCL12 positive ratio was significantly higher. Significant relationship between CXCL12 and CXCR4 was found both in OLK and OSCC. Conclusion. Our results indicated that CXCL12/CXCR4 axis may play roles from early steps of oral malignant transformation and contribute to the progress of oral carcinogenesis.