Although ameloblastoma and adenomatoid odontogenic tumor (AOT) belong to the same group according to the World Health Organization, they show different biologic behaviors. PCNA, an amplifier of cell proliferation, and p53, a tumor suppressor protein, are overexpressed in some odontogenic lesions. The purpose of this study was to immunohistochemically evaluate the expression of p53 and PCNA to clarify the possible role of these proteins in different behaviors of ameloblastoma and AOT. The immunohistochemical expression of PCNA and p53 was determined in 30 solid ameloblastomas and 12 AOTs. Statistical tests including one-way ANOVA, t-test, chi-square, Mann-Whitney U and Kendall were used to analyze the data. All tissue sections (except one specimen of plexiform ameloblastoma) exhibited immunoexpression for p53. PCNA was expressed in all specimens. There was no significant difference in PCNA expression between ameloblastomas and AOTs (P > 0.05). For p53, there was no statistical difference between subtypes of ameloblastomas (P > 0.05), whereas statistical differences were observed between ameloblastomas and AOTs (P < 0.001). There was no statistical difference in PCNA intensity of staining between ameloblastomas and AOTs (P > 0.05), whereas the p53 intensity in ameloblastomas was stronger than AOTs (P < 0.05). Positive correlation between PCNA and p53 was observed. We concluded that PCNA overexpression is not responsible for the difference in clinical behavior of these two lesions, whereas the expression of p53 in ameloblastoma may explain the more aggressive nature of this tumor compared with AOT.