Protein tyrosine kinases (PTKs) play a crucial role in regulating thyroid cell growth and differentiation. The Axl protein is a member of a new family of receptor tyrosine kinases, of which the ligand, Gas6, a protein S-related molecule, recently was proved to be a mitogenic factor for human thyroid cells. To further investigate the involvement of Axl in human thyroid carcinoma, we examined tissues obtained from 81 patients with thyroid carcinomas, 18 with adenomas, and 13 with adenomatous goiters by immunohistochemistry and in situ hybridization. In addition, among the thyroid carcinomas, we compared Axl expression levels with the grade of differentiation and lymph node metastasis of the carcinoma. Axl was expressed faintly in adenomatous goiter and adenomas, but not in normal thyroid tissues. Among the 81 cases of thyroid carcinoma, 70 (86.4%) showed a positive staining for the Axl protein. Immunopositive (+ +) was detected in papillary carcinomas and anaplastic carcinomas. The level of Axl expression, however, had no correlation with the presence of lymph node metastasis in thyroid carcinomas. In situ hybridization also confirmed the presence of axl mRNA in thyroid carcinoma tissues. These findings suggest that Axl expression may be closely involved in human thyroid tumorigenesis.