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The expression of the embryonal and of the differentiational proteins in 12 cases of chordoma and in the notochord of a 4-month-old and a 5-month-old human embryo have been examined immunohistologically by the ABC method using polyclonal antibodies to CEA, AFP, or S-100, and the monoclonal antibody to cytokeratin. It was found that S-100 was expressed in all cases of chordoma and in the notochords examined. CEA and cytokeratin also were found expressed in some cases of chordoma but not in the notochords. These proteins were found expressed more strongly in chordomas without a metastasis than in those with a metastasis. In the metastatic lesions, these proteins were expressed more strongly than in the primary lesions. The antibody to AFP reacted with neither the chordomas nor the notochords tested. These results suggest a possible link between the gene-expression of the tumor cells and the microenvironment in which they are harbored.