Introduction. Systematic anatomical studies corroborate the anatomical complexity of the root canal system. Deviations from the norm such as multiple orifices, apical deltas, accessory canals and other variations are frequent. Objectives. To present clinical reports of mandibular molars with three canals in the mesial root and two in vitro studies of the morphology of these canals, together with a review of the literature. Materials and Methods. Three clinical reports are presented of mandibular molars where three canals in the mesial roots were treated endodontically. Two in vitro studies were performed, one using computerized tomography and the other with scanning electron microscopy, to describe the morphology of the mesial root canals of permanent first molars. The scientific literature on this anatomical situation was also reviewed. Results. The tomographic study found that the prevalence of a third mesial canal in the 27 teeth analysed was 14.81%; the microscopic study of 25 teeth found it to be 12%. The review of the literature encountered that the authors who report cases such as these found prevalences ranging from 1% to 15%. Conclusions. From the teeth analysed in vitro, it is concluded that a third mesial canal may be present in a mandibular first molar in approximately 13% of cases. Clinically, the third canal is difficult to find and exhibits a very variable morphology, which may present anastomosis with the other canals.