The present study investigated the immunohistochemical expression of p53, p63, and p73 in different types of odontogenic cysts (OC), a group of common intraosseous jaw lesions, to provide a better understanding of p53-family functions in odontogenic lesions. We carried out immunohistochemical analysis to evaluate the expression of p53, p63, and p73 in 60 samples of OC, including dentigerous cysts, radicular cysts, orthokeratinized OC, and odontogenic keratocysts (OKC). The epithelial expression of p53-family members was evaluated both in the basal-parabasal and in the superficial layers, measuring the percentage of positive cells and the value of expression intensity. The expression of p53-family members showed a significant difference between the "OKC" and "non-OKC" groups. In particular, p53 positivity in the basal-parabasal layers, as well as p63 positivity in the superficial layers, were more common in OKC (P<0.0001; P=0.0237). p73 expression in the superficial layers was significantly more expressed in the "non-OKC" group (P<0.0001). No significant differences of staining intensity scores were reported between the groups. The Spearman test showed a positive correlation between p53 and p73 expression at the basal-parabasal level in all cysts (r=0.6626; P<0.0001). These results showed a significantly different expression of p53-family members in OC groups, in particular between the "OKC" and "non-OKC" groups, suggesting the existence of a p53-family pathway in the epithelial lining of OC.