Introduction: Glypican-3 is a cell surface protein, a member of glypican family and belongs to agroup of heparin sulfate proteoglycan bound to the cell membrane through a glycosylphosphatidylinositol anchor. GPC3 is involved in the regulation of cell proliferationand morphogenesis. Considering the distinct clinical behavior of odontogenic lesions, the aim of the present study was to investigate the immunohistochemical expressionof GPC3 in DENTIGEROUS CYST, odontogenic keratoCYST and radicular CYST. Materials& Methods: In this descriptive, retrospective, cross-sectional study, 60 tissue samples ofodontogenic CYSTs consist of 20 radicular CYSTs (RC), 20 odontogenic keratoCYSTs(OKC) and 20 DENTIGEROUS CYSTs (DC) were reviewed by immunohistochemistrystaining for GPC3 marker. Results: In this study, both membranous and cytoplasmic expression of glypican-3 wasobserved. GPC3 expression was seen in 60% of OKCs (12/20). No GPC3immunoreactivity was seen in DCs and RCs. Conclusion: A high expression rate of GPC3 was detected in OKC, which might be related to theaggressive behavior and high recurrence rate of OKC; however, further studies arenecessary to confirm this hypothesis.