Introduction: The aim of this study was to analyze and characterize root canal morphology of mandibular molars of the Brazilian population by using cone-beam computed tomography (CBCT). Methods: Patients who required CBCT radiographic examinations as part of their routine examination, diagnosis, and treatment planning were enrolled in the study. A total of 460 healthy, untreated, fully developed mandibular first and second molars were included (234 first molars and 226 second molars). The following observations were recorded: (1) number of roots and their morphology, (2) number of canals per root, (3) C-shaped canals, and (4) primary variations in the morphology of the root canal systems. Results: First molars showed a higher prevalence of 2 canals in the mesial root and 1 in the distal root with 2 separate roots (74%). In the mandibular second molars, the presence of 2 separate roots with 2 canals in the mesial root and 1 canal in the distal root represented 54% of the total. In 32% of the cases, 2 separate roots with 1 canal each in the mesial and distal roots were presented. The incidence of C-shaped canals was 1.7% of first molars and 3.5% of second molars. Conclusions: A higher prevalence of 2 separate roots with 2 canals in the mesial root and 1 canal in the distal root was observed in mandibular first and second molars (74% and 54%, respectively). Also, a lower incidence of C-shaped canals and 3-rooted teeth was observed in a Brazilian population. CBCT is a clinically useful tool for endodontic diagnosis and treatment.397849852