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p53 protein seems to be related to the suppression of cell proliferation. p53-positive tissues seem to have a higher proliferative activity than p53-negative ones. Odontogenic keratocyst (OKC) has a different behavior from other types of cysts because it is more aggressive, with a tendency to recurrence. Twenty-two dentigerous cysts, 24 radicular cysts, and 20 OKCs were used in the present study. Two dentigerous cysts (9.1%), 2 radicular cysts (8.3%), and 9 OKCs (45%) expressed the p53 protein. The differences between the three groups were statistically significant (p = 0.003). In 10 cases of OKCs epithelial dysplasia was found. One of the 10 OKCs without dysplasia and 8 of the 10 OKCs with dysplasia were p53-positive: the difference between the two groups was statistically significant (p = 0.007). The overexpression of p53 protein was not on the other hand correlated with the occurrence of multiple, bilateral, and recurrent OKCs. Moreover the distribution of p53-positive cells was parabasal in contrast with other types of cysts. These qualitative and quantitative differences in proliferative activity in OKCs seem to point to an alteration in cell cycle control.