Background: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a member of CEACAM family and has been reported to be upregulated in various types of human cancer and involved in tumor progression and metastasis. However, the biological roles and clinical significances of CEACAM6 in osteosarcoma still remain to be elucidated. Materials and methods: Real-timePCR, immunohistochemistry and Western blot analysis were used to determine CEACAM6 expression in osteosarcoma cell lines and clinical specimens. Then the clinical relevance of CEACAM6 was analyzed in osteosarcoma. The function of CEACAM6 in osteosarcoma was examined by wound-healing and cell invasion assays, and expression levels of epithelial-mesenchymal transition markers. Results: In the present study, we found that CEACAM6 was markedly upregulated in metastatic osteosarcoma tissues when compared with the nonmetastatic osteosarcoma tissues. Upregulation of CEACAM6 was significantly associated with lung metastasis status (p=0.006) in patients with osteosarcoma. Survival analyses suggested that osteosarcoma patients with high CEACAM6 expression had a significantly shorter overall survival time and lung metastasis-free survival time than those with low CEACAM6 expression. Knockdown of CEACAM6 inhibits osteosarcoma cell migration and invasion. Moreover, silencing CEACAM6 suppressed osteosarcoma cells epithelial-mesenchymal transition. Conclusion: Taken together, this study suggests that CEACAM6 might be a promising biomarker and a potential therapeutic target for the treatment of metastatic osteosarcoma.