The cholesteatoma clinically is a chronic inflammatory disease and the most characteristic histologic finding is the proliferation of the squamous epithelium and the accumulation of the keratin. The hyperproliferative state of the keratinocytes in the cholesteatoma may be related with the inflammatory activity. With the development of cell biology, the studies on the origin and biologic behaviors of the keratinocytes have revealed the hyperproliferative state of the keratinocytes in the cholesteatoma, but the fundamental principles and the pathophysiology of the cholesteatoma have not clarified. The epithelium of the cholesteatoma is composed of both keratinizing and non-keratinizing squamous epithelium with various thicknesses histopathologically, and clinically, depending on the location, the disease expresses different levels of inflammatory and bone destructive activities. Thus, the immunohistochemical analysis of the various proliferative markers, such as PCNA, Ki-67, EGF, EGFR and p53 of the cholesteatoma, was done to study the proliferative activities of the squamous epithelium. The expression of PCNA and Ki-67 in the cholesteatoma were higher than in controls. In the cholesteatoma, the expression of PCNA and Ki-67 were the highest in the thick keratinizing squamous epithelium, the next was the non-keratinizing squamous epithelium, and the thin keratinizing epithelium was last. The expression was higher in the suprabasal layers than in the basal layers and in superficial layers to a some degree of expression could be observed. The expression of EGF and EGFR in the cholesteatoma were higher than in controls, and the highest in the thick keratinizing squamous epithelium. The expression of p53 in the cholesteatoma was also higher than in controls. In conclusion, the cholesteatoma had a more proliferative activity than controls, and the keratinizing epithelium of the cholesteatoma had a stronger proliferative activity than the non-keratinizing epithelium. Since the cholesteatoma possesses a variable degree of proliferative activities depending on its histologic composition, the formation and accumulation of the keratin due to the continuous epithelial growth probably are important element in inducing the inflammation.