To elucidate the pathogenesis of abnormal keratinization in nevus comedonicus, we performed an immunohistochemical study using antikeratin and antifilaggrin (filament-aggregating protein) antibodies. There were no significant differences between nevus comedonicus and normal skin in cytokeratin expression. Although filaggrin was only detected in the granular layer in open comedones, filaggrin was detected in both superficial cells and also intermediate cells in closed comedones, suggesting that filaggrin is involved in the formation of closed comedones. The disorder of terminal differentiation related to filaggrin may play a role in the pathogenesis of abnormal keratinization in nevus comedonicus.