Odontogenic keratocysts (OKC) present an aggressive course with a marked tendency to recurrence. The epithelium of OKC is thought to have an intrinsic growth potential and has been shown to present a higher rate of proliferation as compared to other types of cyst. bcl-2 has a role in the extension of cell survival. The objective of the present study was to evaluate the bcl-2 protein expression in different odontogenic cysts. A total of 19 dentigerous cysts (DC), 20 radicular cysts (RC) and 14 OKC were used in the present study. DC and RC showed an almost complete negativity for bcl-2. OKC, on the other hand, presented in all cases a strong positivity in the cells of the basal layer, with, in most cases, more than 50% of the cells positive. This bcl-2 positivity of the basal layer of OKC could point to an abnormal control of the cell cycle. The bcl-2 protein overexpression could then produce an increase in the survival of the epithelial cells, and this increased lifespan could, in turn, lead to the peculiar aggressive growth pattern of OKC. Moreover the bcl-2 staining can be useful to differentiate OKC from other types of odontogenic cysts.