Mucosal melanocyte distribution in the human lower lip was analyzed immunopathologically using a wide selection of 195 surgical specimens. An age-related increase of mucosal melanocyte distribution was observed in the human lower lip by Fontana-Masson argentaffin stain and S-100 protein immunoreactivity. The mean number of mucosal melanocytes increased gradually with advancing age. A large number of them was found at or beyond the seventh decade of life in both sexes, which was statistically significant compared with those in all other decades (p < 0.01 or < 0.05). In addition, the sex difference in mucosal melanocyte density was statistically significant (p < 0.001) in each decade (men > women). These results suggest that physiological changes in mucosal melanocyte distribution are dependent upon aging and sex difference, and may play an important role in development of melanocytic lesions such as senile lentigo, pigmented nevi, and also intraepithelial malignant melanomas.