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Rushton bodies are known to be the aberrant keratinization and calcification in the epithelium of odontogenic cyst, which are similar to the features of calcifying odontogenic cyst and pilomatricoma. However, the pathogenetic mechanism of keratinization and calcification of Rushton bodies has not been clearly elucidated. Here, a case of Rushton bodies found in dentigerous cyst was examined by immunohistochemical method using antisera of PCNA, pAKT, HIF, PIM1, and PARP. The globular keratinization in lamellate fashion showed weak birefringency under polarizing microscope, and the Rushton bodies frequently underwent the dystrophic calcification. The polygonal keratinocytes of Rushton bodies were strongly positive for HIF and PARP, and the cyst epithelium was diffusely positive for pAKT and PIM1. Particularly, the cyst epithelium was hyperplastic and focally invaginated into cyst wall with positive reaction of PCNA. These findings may indicate the active response of odontogenic epithelium against the apoptotic stress of the cyst, producing the globular keratinization and irregular calcification in the polygonal keratinocytes. Therefore, it is presumed that the lamellate keratinization and dystrophic calcification of Rushton bodies are aberrant products of retrograding keratinocytes slowly undergoing apoptotic progresses similar to the phenomena of the ghost cells in calcifying odontogenic cyst and pilomatricoma, and also may have a potential for oncogenic proliferation.