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Mandibular premolars exhibit intricate and diverse root canal anatomy, presenting substantial challenges in endodontic treatment. Uncommon variations, such as the presence of three canals, demand meticulous diagnostic and therapeutic approaches to mitigate the risk of overlooking canals and subsequent treatment failure. This case report highlights three cases of mandibular premolars exhibiting a rare root canal configuration with one mesial and two distal canals, successfully managed using cone beam computed tomography (CBCT) for accurate diagnosis and ultrasonic activation for disinfection. The findings underscore the significance of utilizing three-dimensional imaging and precise canal identification in addressing anatomical anomalies in mandibular premolars, which have been sparsely documented in the existing literature. This report aims to contribute to understanding and managing the rare and complex root canal configurations in endodontics., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, A et al.)