Although benign, ameloblastomas are locally invasive and destructive tumors of the jawbones. The glypicans comprise a family of glycosylphosphatidylinositol-anchored proteoglycans that, by virtue of their cell-surface localization and heparin sulfate chain composition, might regulate the response of cells to numerous heparin-binding growth factors, cell adhesion molecules, and extracellular matrix components. The expression of glypican-1 is differentially altered among different types of malignancies, suggesting a possible role in the tumorigenesis and biological behavior of these neoplasms. The aim of this study was to determine the expression of glypican-1 and then hypothesize the possible role that this protein may play in the biological behavior of ameloblastomas. We assessed the presence of glypican-1 by immunohistochemical staining analyses in a series of 80 cases of different types of ameloblastomas. Desmoplastic ameloblastomas exhibited the highest expression of glypican-1 (100%), followed by the peripheral (66%), solid/multicystic (51.2%), and unicystic (47.2%) types, showing statistically significant differences among them (P<0.001). Differences detected in glypican-1 expression among different subtypes of ameloblastomas, could be suggesting a possible association with their different biological behavior.