The purpose of this study was to investigate a case of calcifying odontogenic cyst (COC) in which numerous calcifications were observed not only in the lining epithelium, but also in the cyst wall, using cytokeratins 13 (CK13), 19 (CK19), and core binding factor a-1 (cbfa-1) as primary antibodies. Cells of Malassez's epithelial rest were stained as controls. Cells of the epithelial nests in the cyst wall were reactive for CK13, but their CK19 staining was similar to that observed in the lining epithelial cells. Calcifying nodules were reactive only for CK13. Cells of Malassez's epithelial rest were reactive for CK19 but not for CK13. Cbfa-1 positive reactivity was observed only in nuclei of spindle cells in the periodontal ligament. CK13 was positive superficial to the prickle cells. CK19 was positive in the basal cells of the oral mucosa. In the lining epithelium of the cyst, the expressions of CK13 and CK19 were similar to their immunoreactions in the oral mucosa. These results suggest that the odontogenic epithelium differentiated into squamous epithelial cells, which began as ghost cells in the COC, and that this process depended on the dystrophic calcification of differentiated odontogenic epithelial cells, not of osteogenic cells.