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Success in root canal treatment is achieved after thorough cleaning, shaping, and obturation of the root canal system. The main reason for the unsuccessful root canal treatment is the lack of knowledge of anatomic variations and the characteristics of the different teeth. A mandibular first molar with the third distal canal is very rare, and its occurrence has been reported to be around 0.6%. This article presents the endodontic management of the first mandibular molar with mid-distal canal, which is not quite common. How to cite this article: Kohli A, Mittal R, Tandan M. Endodontic Management of a Permanent Mandibular First Molar with Five Root Canals Aided by Cone-beam Computed Tomography: A Case Report. Cons Dent Endod J 2020;5(2):48–51.