Calcifying epithelial odontogenic tumor, also known as Pindborg tumor, is a rare benign tumor with locally aggressive behavior. It is characterized by squamous epithelial cells, calcifications, and eosinophilic deposits that have been identified as amyloid. We report a case of calcifying epithelial odontogenic tumor and investigate the nature of the amyloid, using histologic, immunohistochemical, and ultrastructural studies. The amyloid was immunohistochemically negative for basement membrane components and positive for all cytokeratin stains performed (cocktail of cytokeratins 1, 5, 6, 8, 13, and 16, and cytokeratins AE1 and AE3). The amyloid stained focally in a glandular-like pattern, reminiscent of the epithelial glandlike structures of the tumor. We conclude that the amyloid is derived from filamentous degeneration of keratin filaments that originate from the tumor squamous epithelium. The keratin degeneration is part of a developmental or aging process that the tumor undergoes.