Although the prognosis is generally good for patients with papillary thyroid carcinoma, gross nodal metastasis of carcinoma has a poor prognosis. It is necessary to clarify how carcinoma progresses to gross nodal metastasis in order to establish a cure. The adhesion molecule integrin beta-4 is considered to be related to cell migration and metastasis in many carcinomas. In the present study, we examined integrin beta-4 expression in 65 cases of human papillary thyroid carcinoma using immunohistochemical methods. Expression of integrin beta-4 was found in all papillary carcinomas, but in few normal thyrocytes. Interestingly, integrin beta-4 expression in the carcinomas with gross (greater than or equal to3 cm) lymph node metastasis was significantly higher than that in carcinomas with small (<3 cm) or no lymph node metastasis. These results suggest that integrin beta-4 expression in thyroid carcinoma may play a role in the development of gross lymph node metastasis of papillary carcinomas.