The aim of this study was to evaluate the immunoexpression of claudin-1 and Nm23-H1 in metastatic and nonmetastatic lower lip squamous-cell carcinoma (LLSCC). Twenty LLSCCs with regional nodal metastasis and 20 LLSCCs without metastases were selected. The percentage of claudin-1 staining and the staining intensity and percentage of Nm23-H1 staining in each tumor core were assessed. Metastatic tumors exhibited higher expression of claudin-1 than nonmetastatic tumors (P = 0.030). Similarly, stage III and IV LLSCCs showed higher expression of claudin-1 than stages I and II (P = 0.026). The percentage of claudin-1 staining was scored as 2 in most well-differentiated and moderately differentiated tumors, whereas poorly differentiated tumors showed a relatively similar distribution of scores 2, 1, and 0 (P = 0.648). Regarding Nm23-H1, there was a predominance of negative cases for both metastatic and nonmetastatic tumors (P = 0.235). In addition, no significant differences in the percentage of Nm23-H1-negative and Nm23-H1-positive cases were observed regarding the clinical staging (P = 0.430) and the histologic grading of malignancy (P = 0.702). The results of this study suggest an important role of claudin-1 in the development of metastasis in LLSCCs. In contrast, the present findings do not support a significant role of Nm23-H1 in metastasis suppression of LLSCC.