Objective To investigate the expression of c-met in tall cell variant of papillary thyroid carcinoma, and to compare it with other types of thyroid carcinoma and benign thyroid tissue. Methods The expressions of c-met in 60 cases of thyroid specimens were tested by immunohistochemical staining. Results The levels of expressed c-met in tall cell variant specimens were significantly higher than those in other types of papillary thyroid carcinoma and benign thyroid tissue. c-met expressions were significantly different in the following pairs of types: tall cell variant vs common papillary carcinoma of thyroid (P=0.000 1), tall cell variant vs follicular variant papillary thyroid carcinoma (P=0.000 1), and tall cell variant vs benign thyroid tissue (P=0.000 1). In addition, for all types of papillary carcinomas evaluated, c-met expression was significantly higher in specimens with extracapsular spread (P=0.010 0) and skeletal muscle invasion (P=0.020 0). Conclusion The high expression of c-met is a significant marker for tall cell variant papillary carcinoma of thyroid and its invasive behavior. This finding may explain the unusually aggressive behavior of this tumor and suggest a role for c-met in the early identification of patients with tall cell variant thyroid carcinoma.