We previously showed that the preservation of neural adhesion molecule (NCAM) in differentiated thyroid carcinoma is an important indicator for a higher risk of distant metastasis. In the present study, we further demonstrated that forced NCAM-140 isoform expression in human thyroid cancer cells could lead to aggressive growth by enhancing migration and anchorage-independent growth, and exhibiting partial features of epithelial mesenchymal transition. More extensive distant metastasis was also noted in an animal xenograft model when NCAM-expressing thyroid cancer cells were introduced into mice intravascularly. Bioinformatic analysis of NCAM-associated expression profiles predicted a highly interactive protein network, which further implies potential molecular mechanisms underlying the metastatic processes of thyroid cancer.