Objectives: The orthokeratinized jaw cyst (OJC) is presently recognized as distinct from the odontogenic keratocyst (OKC). While OKC is known for its potentially aggressive biological behaviour, OJC shows limited growth potential and has a lower recurrence rate. The histomorphologic features of the lining epithelia of OKC and OJC suggest that characteristics of the cyst linings probably play a dominant role in determining the biological behaviour. The aim of this study was to investigate whether a significant difference exists in the proliferation index of the epithelial cells in OKC and OJC, by using the proliferation marker, Ki-67. Methods: Ki-67 immunoreactivity in OKC (n=16) and OJC (n=14) was studied using a biotin-streptavidin-immunoperoxidase technique. Ki-67+ epithelial cells were counted manually in 10 high power fields in each case. Two observers using a multi-headed microscope carried out the evaluation simultaneously. The compare the mean labeling index of Ki-67 between the two samples we used the Mann-Whitney U test. P-values of < 0.05 were regarded as significant. Results: The number of Ki-67+ cells in OKC (mean=352.5±266.16) was significantly greater than OJC (mean=130.5±117.53; P = 0.01). The Ki-67+ cells showed a predominantly suprabasal distribution in OKC and OJC. Comparison of Ki-67 expression within the basal layer, revealed no significant difference between OKC (mean=68.2±66.6) and OJC (mean=34.9±34.9; P = 0.15). OJC was more frequently associated with an impacted tooth and showed no racial predilection. There was no significant difference in the age and gender of the patients. Conclusions: The results are consistent with OKC having greater proliferative capacity than OJC and thereby provide a possible molecular basis for the difference in clinical behaviour between the two entities. The findings of this study also shed light on the true nature of the OJC, suggesting that the majority represent dentigerous cysts with orthokeratosis.