Separation of the epithelial lining from the underlying connective tissue wall has been a frequently observed and unique feature in odontogenic keratocysts (OKC), but not in other odontogenic cysts nor neoplasms. No study on OKC has been reported evaluating the role of type VII Collagen, the anchoring fibrils, which function in stabilising the epithelial structure. The purpose of this study was to assess the role of type VII collagen in the fragility of the epithelium leading to a high recurrence rate in OKCs.Immunohistochemical staining with Abcam® Monoclonal Mouse Anti-Collagen VII Antibody [LH7.2] (used at a dilution of 1:200) on 30 tissues of OKC. The chi-square test was applied to confirm the statistical significance between the control and test groups. The frequencies of the pattern of distribution for the staining characteristics of collagen VII were calculated in the OKC samples.Out of the 30 OKC samples 22 (73.3%) showed negative staining for type VII Collagen. Among the infected cases, 7 showed a positive basement membrane staining and one of the non-infected OKC showed positive basement membrane staining. However, none of the syndrome associated or recurrent OKCs showed any evidence of type VII collagen reactivity.Considering the distribution of type VII collagen in OKCs it can be concluded that type VII collagen expression is altered in OKCs, leading to destabilisation of the epithelium connective tissue interface thus rendering the epithelium-connective tissue interface fragile. Key words:Type VII Collagen, Odontogenic Keratocyst, Basal Lamina, Immunohistochemistry.