The epithelioid features seen in chordoma are unique among mesenchymal tumours. However, no detailed analysis regarding cell-cell communication has been conducted in this epithelioid tumour. The aims of this study were to investigate cell-cell communication in chordoma.By means of immunohistochemical techniques that incorporated a panel of monoclonal antibodies against cell adhesion molecules (CAMs), including E-cadherin, alpha-catenin, beta-catenin, gamma-catenin, and neural cell adhesion molecule (NCAM), the expression of CAMs was studied in 15 specimens of chordoma and eight specimens of chondrosarcoma.Most chordoma specimens showed some positive immunoreactivity for all the CAMs examined. For the various CAMs investigated, between two and five cases showed diffuse immunoreactions, indicating well preserved expression. Well preserved expression of all the CAMs examined was limited to only one case, thus indicating that the expression of CAMs was decreased in most of the chordoma specimens; however, no significant correlation was found between the decreased expression of CAMs and the histological grade of malignancy, cellular growth pattern, or clinical parameters in chordoma. In chondrosarcoma, only a few specimens showed positive immunoreactivity for CAMs and the expression of E-cadherin, beta-catenin, gamma-catenin, and NCAM was seen more frequently in the chordoma specimens than in the chondrosarcoma specimens.These results suggest that the expression of CAMs is associated with the formation and maintenance of chordoma tissue architecture, just as it is in other epithelial tumours or normal tissue. Immunohistochemistry for CAMs was found to be of diagnostic value for discriminating chordoma from chondrosarcoma, and these markers could be used along with the cytokeratins, which are already used for this purpose.