This study was aimed to evaluate the prevalence of metaplastic changes in the epithelium of radicular cysts and to investigate how they relate to the clinical and radiographic characteristics of the cysts, based on a large series of radicular cysts. Biopsies of cysts of endodontic origin that were examined at the Department of Oral Pathology between 2004 and 2011 have been re-evaluated for this study. Only cases that were re-confirmed with clinical and histological diagnoses of a radicular or residual radicular cyst were included. The included cases were evaluated for the prevalence of metaplastic changes in the form of mucous secreting cells (MSC) or ciliated cells (CC). The relations between the metaplastic changes and the cyst type (radicular or residual radicular), as well as demographic, clinical and radiographic parameters, were statistically evaluated using Fischer and chi-square tests. Significance was set at p<0.05. A total of 711 cysts were included: 677 were radicular cysts (95%) and 34 (5%) were residual radicular cysts. 23 cases had histopathological diagnoses other than radicular or residual radicular cysts and were excluded from the study. MSC were present in 47 (6.6%) cysts. MSC were significantly more common in residual radicular cysts than in radicular cysts [8 (23.5%) and 39 (5.8%), respectively; p<0.001]. MSC-containing cysts were commonly found in asymptomatic patients (10.5%, p<0.001), and usually presented with well-defined radiographic borders (7.2%, p<0.05). CC were present in 34 (4.8%) cysts, with a markedly high prevalence in the maxillary molar sextant (15%, p<0.001). In the epithelium of radicular and residual radicular cysts the presence of specific metaplastic changes may be related to cyst type, symptomatology, radiographic findings and tooth location.