Objective: To investigate the expression of activated-leukocyte adhesion molecule (ALCAM) in thyroid cancer tissue and the clinical significance. Methods: ALCAM expressions in 52 samples of paired thyroid cancer and adjacent normal thyroid tissues were detected by immuohistochemical staining. The ALCAM expression difference between the two types of tissues was compared, and relations of ALCAM expression with clinicopathologic features and prognosis of the thyroid cancer patients were analyzed. Results: The positive ALCAM expression rate in thyroid cancer tissue was significantly higher than that in adjacent normal thyroid tissue (71.2% vs. 34.6%, P<0.05), but in thyroid cancer tissue, the lower ALCAM expression was associated with poorer histopathological differentiation of the thyroid cancer, and shorter 5-year overall survival of the patients (both P<0.01). Conclusion: Increased ALCAM expression may be involved with the occurrence and development of thyroid cancer. However, the phenomenon of ALCAM expression contrarily reduced in tumor tissues from highly malignant and poor prognostic thyroid cancer is speculated to be related to its detachment and release into the circulation.