Co-expression of cytokeratin and vimentin has been traditionally associated with a few select tumors. However, this phenomenon is being recognized in a wider range of tumors. Twenty-one canine primary pulmonary epithelial neoplasms were evaluated for the co-expression of cytokeratin and vimentin. The histologic pattern and grade, and an immunohistochemical grade for cytokeratin and vimentin staining, were determined for each neoplasm. Adenocarcinomas predominated, and histologically, most tumors were grade II. All of the neoplasms stained positive for cytokeratin, while only 8 (38%) stained positive for both vimentin and cytokeratin. Papillary adenocarcinomas were consistently vimentin negative. The anaplastic histologic pattern had significantly more vimentin staining than the other histologic patterns. There was no significant difference in histologic grade or grading criteria between those tumors that stained with vimentin and those that did not. The present study established that cytokeratin and vimentin co-expression occurs in canine primary pulmonary epithelial tumors at a similar frequency to human pulmonary neoplasms. Further investigation will be needed to characterize the significance of this finding, particularly with respect to prognosis.