During palatine rugae development in mice, a cell cluster appeared transiently in the palatine rugae epithelium. The characteristics of these cells were examined histologically and immunohistochemically for anti-cytokeratin (CK) and anti-protein gene product 9.5 (PGP9.5) antibodies using mice from embryonic day 15 (E15) to postnatal day 1 (PN1). At E15, the epithelium of both palatine rugae located in the anterior portion and inter-rugae area consisted of 2-3 cell layers, and palatine rugae have papillae under the epithelium. However, palatine rugae located in the posterior portion have cell clusters in the epithelium. These cells expressed immunopositive reactions for anti-CK18, although they did not react with anti-CK14. Under the anti-CK18 immunopositive cell cluster in palatine rugae epithelium, anti-PGP9.5 immunoreactivity was observed in papillae. Moreover, the basal cells of the cell cluster showed anti-CK7 immunoreactivity. The cell cluster in palatine rugae epithelium disappeared gradually and anti-CK18 immunopositive cells also disappeared. However, anti-PGP9.5 immunoreactivity in the papilla was maintained after the disappearance of anti-CK18 immunoactivity in the palatine rugae epithelium. At PN1, the epithelium of the palate, including the palatine rugae, was stratified and keratinized. These findings suggested that the cell cluster in the palatine rugae epithelium may be considered as a taste bud-like structure according to the expression pattern for anti-CK and may play an important role in nerve innervation to the papilla under the palatine rugae epithelium.