Background Several nonendodontic diseases can occur in the periapical region, resembling endodontic inflammatory conditions. Therefore, the aim of the present study was to determine the frequency of nonendodontic periapical lesions diagnosed in a Brazilian population. Material and Methods The files of two Oral Pathology laboratories were reviewed and all cases including at least one clinical diagnosis of endodontic periapical lesions were selected for the study. After initial selection, demographic and clinical data, clinical diagnosis and final diagnosis were reviewed and tabulated. Final diagnosis included endodontic periapical lesions, and benign and malignant nonendodontic periapical lesions. Data were descriptively and comparatively analyzed among the three groups, with a significance level of 5% ( p <0.05). Results Nonendodontic periapical lesions were identified in 208 (19%) out of the 1.125 registries included in the final sample. Benign nonendodontic periapical lesions (200 cases, 18%) were mostly odontogenic keratocysts, ameloblastomas, nasopalatine cysts, dentigerous cysts, glandular odontogenic cysts, and benign fibroosseous lesions. Malignant nonendodontic periapical lesions (8 cases, 1%) included carcinomas, adenocarcinomas, and melanoma. In general, nonendodontic periapical lesions were more common in males and in the posterior mandible ( p >0.05). Conclusions The frequency of nonendodontic periapical lesions was high and, although the general distribution was similar to the results from other populations, some features were probably associated with the profile of the studied populations and to the methods applied in the present study. Knowledge on differential diagnosis of endodontic and nonendodontic periapical lesions is essential to avoid unnecessary treatments and diagnostic delay in routine dental practice. Key words: Differential diagnosis, nonendodontic, periapical lesion, pulp necrosis.