Middle ear cholesteatoma is destructive to auditory ossicles and temporal bone, and treatment usually requires surgical removal of all epithelial content. Epidermal growth factor (EGF) can stimulate the growth and differentiation of a variety of mammalian cells, including epithelial cells. Our study used the avidin-biotin complex technique to evaluate the expression of EGF in 40 cases of middle ear cholesteatoma (active cholesteatoma, 31 cases; inactive cholesteatoma, 9 cases) and 34 normal postauricular skin samples. In middle ear cholesteatoma, EGF was expressed in squamous epithelium in 21 cases (53%), fibroblasts in two cases (5%), and cholesteatoma endothelium in two cases (5%). In normal postauricular skin, EGF was expressed in squamous epithelium in 14 samples (41%), fibroblasts in one sample (3%), and endothelium in none. No statistical difference in EGF expression was found between cholesteatoma and normal postauricular skin samples. These results show that the distribution of EGF in middle ear cholesteatoma is not deranged and that the progression of cholesteatoma might be induced by the release of factors from the cholesteatoma matrix via autocrine stimulation, or by inflammatory cells of the subepithelial tissue through paracrine stimulation, or in both of these ways.