Although the prognosis of differentiated thyroid cancer is generally favorable, some patients develop progressive disease resulting in a life-threatening condition and occasionally fatal outcome. CD44v6 is known to be a marker linked to distant metastasis in several types of human malignancy. In the present study, we analyzed the expression of CD44v6 in primary tumors and recurrent disease in the regional lymph node and evaluated its correlation with clinical variables and prognostic factors in patients with differentiated thyroid cancer. CD44v6 expression in the primary tumor was immunohistochemically detected in 58 of 79 patients (73%). Among parameters investigated, none except patient age showed a correlation with CD44v6 expression; the rate of positivity for CD44v6 was significantly higher (p=0.023) in patients aged 50 years or less than in those aged over 50 years. During the follow-up period, 14 patients were found to have recurrent cancer in regional lymph nodes, and among these, distant metastases were later detected in bones and/or lungs in 6 patients. Although an overall correlation between the expression of CD44v6 in the regional recurrent site and in distant metastasis was not statistically significant, there was a tendency that patients with positive CD44v6 in the regional lymph nodes subsequently developed distant matastases. CD44v6 appears to play an important role in tumor progression in patients with differentiated thyroid cancer, particularly in terms of recurrent disease in regional lymph nodes.