The aim of this study was to investigate the expression of the p63 gene in normal human tooth buds at different gestational stages. This is the first detailed study of p63 expression in normal human prenatal tooth primordia. The material consisted of sections of the midaxial tissue block from the cranial base of three human fetuses of gestational ages (GA) 11, 15, and 21 weeks. The sections included tooth primordia representing cap stages and bell stages of human tooth morphogenesis. In the present study, immunostaining was carried out using the primary antibody, monoclonal mouse anti human p63 protein, clone 4A4. The sections were counterstained with hematoxylin Mayer. p63 immunoreactivity was identified by microscopy. The study showed a positive reaction of p63 in both the cap stage and the bell stage. In both stages, positivity was observed in the cells of the oral mucosa, the inner and outer enamel epithelium, and in the primary and secondary dental lamina. In the early cap stage, there is a strong positive reaction to p63 in the enamel knot, but not in the late cap stage. We suggest that p63 may have an important regulatory function in the enamel knot.