Objectives: Keratocystic odontogenic tumors (KOTs), also known as odontogenic keratocysts, were recently classified as a benign neoplasia due to the aggressive clinical behavior. Although several studies have shown the high proliferative activity of the epithelial lining, few studies have evaluated apoptosis in KOTs. Therefore, the aim of this study is to evaluate and compare the proliferation index (PI) and the apoptotic index (AI) of the epithelial lining in sporadic KOTs, KOTs associated with the Nevoid Basal Cell Carcinoma Syndrome (NBCCS KOTs), and dentigerous cysts. Material and methods: A total of 11 sporadic KOTs, 15 NBCCS KOTs, and 11 dentigerous cysts were evaluated. The PI was assessed by immunohistochemical detection of the cell proliferation marker Ki-67. The AI was assessed by morphological evaluation of sections stained by methyl green-pyronin. The TUNEL assay was used to confirm the occurrence of apoptosis. Differences in the PI and the AI between sporadic KOTs, NBCCS KOTs, and dentigerous cysts were analyzed using the Kruskal-Wallis test. Differences in the PI and the AI between the epithelial layers of each lesion were analyzed using the Wilcoxon test. Results: The PI and AI were higher in sporadic and NBCCS KOTs than in dentigerous cysts. No difference in these indexes was observed between sporadic and NBCCS KOTs. In dentigerous cysts, the PI was higher in the basal layer. In sporadic and NBCCS KOTs, the PI was higher in suprabasal layer. No difference in the AI was observed between the basal layer and the suprabasal layer in the three lesions. The AI was higher in the superficial layer of sporadic and NBCCS KOTs. Conclusions: The present study demonstrates that the epithelial lining of KOTs shows a distinct pattern of cell proliferation and apoptosis, reflecting its high cell turnover and reinforcing its classification as an odontogenic tumor.