The objective of this study was to assess the prevalence of odontogenic cysts (OCs) in Sicily and evaluate their distribution during a 20-year period. A cross-sectional retrospective study was carried out in 1,310 cysts of the jaw diagnosed in 12,197 individuals, who consecutively attended the Odontostomatologic Clinic of Palermo from 1986 to 2005. 1,273 cysts were classified as odontogenic, whereas only 37 were non-odontogenic. In the former group, the most frequent lesions were radicular cysts (84.5%), followed by dentigerous OCs (11.4%). Inflammatory radicular cysts were observed more in male gender, younger age at diagnosis and anterior maxilla as site of presentation. Unlike dentigerous cysts, the frequency of radicular cysts decreased from 10.4% in 1986-1995 to about 8% in 1996-2005 (P < 0.0001). Inflammatory radicular cysts are the most represented group among OCs in our area with a higher prevalence than that reported in other countries. The decreasing epidemiologic trend with time could be attributed to the possible changes in individual oral health behavior.