Background Odontogenic keratocyst (OKC) is a development cyst, of odontogenic origin, that differs from other entities by its infiltrating and aggressive biological behavior. Among conservative treatments for large lesions, surgical decompression stands out, with a variable recurrence rate. Aim: To evaluate the histological effects of decompression treatment on OKC, including cell proliferation and apoptosis of epithelial cyst. Material and Methods 21 OKC cases were included. Samples were taken before and after surgical decompression for histological evaluation and immunohistochemical staining of Ki-67, MCM4/7, Bax and Bcl2. Data were analyzed and compared using Student’s t and Wilcoxon tests for related samples, and p values <0,05 were considered statistically significant. Results After decompression treatment an increase in inflammation of the cystic wall ( p =0,029), loss of parakeratinization of the epithelium ( p =0,007) and absence of palisade cell distribution in the basal layer were observed ( p =0,002). There were no statistically significant changes in the expression of Ki-67 ( p =0,323), MCM4/7 ( p =0,079), Bax ( p =0,392) or Bcl-2 when compared before and after decompression. Conclusions Surgical decompression generates histological structural changes in OKC both in the epithelium and connective wall, however, these findings do not seem to alter induction of the cell cycle or epithelial apoptosis. Key words: Odontogenic keratocyst, MCM, Bax, Bcl2, Ki-67, apoptosis, decompression.