It is not known whether the presence of an impacted tooth or the radiographic types in an odontogenic keratocyst (OKC) change the clinical biologic behavior and therapeutic approaches. This study evaluated the comparative proliferative activity and apoptosis in OKC associated with or without an impacted tooth, as well as between the unilocular and multilocular OKC varieties. Immunohistochemical expression of Ki-67 as a proliferation marker and the apoptotic reactions were assessed by the TUNEL method for 32 cases of OKC (OKC with impacted tooth, n=16; OKC without impacted tooth, n=16) and 10 cases of dentigerous cyst (DC). OKC showed a greater proliferative potential and more apoptotic reactions than DC. In particular, OKC contained proliferating and apoptotic cells situated predominantly in the suprabasal and superficial layers, respectively. However, no significant difference was found between OKC associated with or without impacted tooth, or between the unilocular and multilocular OKC varieties, in terms of proliferative activity or apoptosis. In conclusion, OKC is characterized by an increase in both cell proliferation and apoptosis, suggesting a unique proliferative and differentiation process. It is believed that incomplete removal or other contributing factors, rather than intrinsic growth or apoptosis, may be the main reasons for the aggressive biologic behavior or recurrence in multilocular OKC.