Epigenetic silencing of gene expression by promoter CpG island hypermethylation is promoted by the enzymes, DNA methyltransferases (DNMTs). DNMT3a is mainly involved in de novo methylation, whereas DNMT1 acts mainly as a maintenance methyltransferase. The purpose of this study was to investigate the immunoexpression of DNMT1 and DNMT3a in a set of odontogenic cysts and tumours. Formalin-fixed and paraffin-embedded tissue samples of eight radicular cysts, 10 odontogenic keratocysts (OKC), eight adenomatoid odontogenic tumours (AOT), 16 ameloblastomas and eight samples of normal mucosae were included in the study. The DNMT1 and DNMT3a proteins were identified by using a highly sensitive polymer-based system. We found that the normal oral mucosa, OKC, AOT, radicular cyst and ameloblastomas samples showed a widespread nuclear and cytoplasmic immunopositivity for DNMT1. Some radicular cysts, ameloblastomas, AOT and OKC samples presented a positive cytoplasmic reaction for DNMT3a, while negative staining was observed in the normal oral mucosa. Nuclear positivity was found only in the suprabasal cell layers of three OKC samples. Our study shows an increased expression of DNMT3a in odontogenic cysts and tumours, confirming that epigenetic mechanisms are involved in the development of these tumours.