The purpose of this study was to evaluate whether marsupialization treatment induces changes in the histology of odontogenic keratocyst epithelium and to compare our experience with the literature. A retrospective revision of histological samples was performed. 5 patients with odontogenic keratocyst treated with marsupialization follow by enucleation were selected. Histologic evaluation analyzed the changes in the keratocyst epithelium after marsupialization in terms of type of keratinization, thickness of the epithelium and connective tissue, the presence of acanthosis, the presence and grade of fibrosis, the type and grade of inflammation and the presence and number of mitotic figures and daughter cysts. In our case series, a variation of para-keratinized into ortho-keratinized keratocyst was found in one case, and no significant increases were observed in the epithelium and capsule thickness, or even in the level of inflammation. However, we observed an increase in fibrosis and qualitative changes in inflammation type. Minor and major histological changes were associated with reduction in cyst volume, which resulted in a simpler and less invasive cystic enucleation after marsupialization.