Abstract The successful execution of endodontic therapy relies on the understanding and awareness of potential anatomical variations within the root canal system to effectively locate, prepare, and seal the root canals. There are significant variations and unique root canal anatomies in mandibular premolars, which can pose diagnostic challenges. Typically, mandibular premolars feature a single root with a single canal, while the occurrence of two or three canals in distinct roots is uncommon. This case report presents two instances of endodontic treatment for mandibular premolars with two and three root canals.