Oral candidiasis presents characteristic histopathological findings. The mucous epithelium at the site of candidiasis is covered by a hyperkeratinized layer. But, the factors leading to hyperkeratosis in candidiasis were unknown. To investigate the factors which led to hyperkeratosis in oral candidiasis, we histopathologicaly, histochemicaly, and ultrastructualy observed the morphological alteration of the epithelial tissue, and studied the factors in connection with those changes immunohistochemically.Candidiasis group (8 cases of papilloma, 5 cases of verrucous hyperplasia), non-candidiasis group (8 cases of papilloma, 7 cases of verrucous hyperplasia), and 5 subjects with normal oral mucosa were selected. Ultrastructually, Candidal hyphe internalized into the epithelial cytoplasmic vacuole resembling endocytosis.Destruction of desmosomal cell junction and deficit of tonofilament was also observed at the tip of the hypha. Immunohistochemistry, weaker expression for E-cadherin was seen in the candidiasis group. Strong positive Ecadherin reaction was seen along the insertion sites of the hyphae. CK13 was negative in non-candidiasis group, and weakly positive in candidiasis groups in the basal layer, respectively. Weakly positive EGFR reactions were observed in the prickle layer in candidiasis group. Inflammatory reaction with NE, CD68, COX-2, CD105 and Ki-67 were markedly observed in candidiasis group.The above result suggested that the hyperkeratosis in oral candidiasis was related with Ecadherin in connection with adhesion and penetration of Candidal hyphae and the precocious expression of the stratified squamous epithelium later differentiated marker CK13. Furthermore, it was surmised that inflammatory response by Candidal hyphae invasion itself led to hyperkeratosis.