Background: To identify the prevalence and clinicopathological profile of calcifying odontogenic cysts (COC) stored at an oral pathology service, and to analyze the immunoexpression of cyclooxygenase 2 (COX-2) and cyclin D1 (CD1) in these cysts. Material and Methods: After a retrospective analysis (1990-2016) carried out to identify cases of COC, a sample of 12 cases was selected for immunohistochemical analysis of COX-2 and CD1 by the immunoperoxidase technique. Protein expression was evaluated semiquantitatively by attributing a score of 0 to 3 (0 = no staining; 1 = 1-25%; 2 = 26-50%, and 3 = >51% immunopositive cells). Results: Twenty cases of COC were diagnosed over the study period. These cysts were more common in the posterior mandible and in men (male-to-female ratio of 1.2:1), with a mean age of 29.9 years. Among the 12 cases analyzed, immunoexpression of COX-2 was observed only in the inflammatory infiltrate in 50% of the cysts (n = 6). Protein CD1 was detected (score 1) in 66.6% of cases (n = 8), and COX-2 was negative in 50% (n = 6). Conclusions: The prevalence of COC among all odontogenic cysts was 3.5%, representing an uncommon lesion. Immunohistochemical analysis suggested that COX-2 does not participate in lesion progression. The cell proliferation index of COC was low, as demonstrated by the expression of CD1, suggesting a proliferative profile compatible with more indolent lesions