The squamous epithelium invading the middle ear markedly alters its growth properties and cause a complex disease known as cholesteatoma. Unless surgically removed, the keratinizing epithelium can results in complication through bone destruction. Both the etiology and pathogenesis of cholesteatoma seem to be related to the epithelial cell migration, proliferation, and differentiation. But the destructive life threatening process is not understood. Thransforming growth factor alpha is known to be produced by normal keratinocyte and to acts on EGFR factor alpha is known to be produced by normal human keratinocyte and to acts on EGFR and to stimulate their proliferation. Authors observed the distribution pattern of EGFR and TGF-α in cholesteatoma and normal meatal skin after immunohistochemical stain. EGFR was highly expressed in the basal layer of the epodermis of normal meatal skin. In the majority of chlosteatoma, expression of EGFR was not not confined to the basal layer but persisted in suprabasal layer. TGF-α was consistently stronger in cholesteatoma than in normal meatal skin. For infiltration of immune cells, the stroma of cholesteatoma stained positively for TGF-α. These data may be consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF-α contributing to its unrestrained growth in the middle ear cavity.