Successful endodontic therapy depends on understanding, knowledge and possible anatomical variations of the root canal system to locate, prepare and obturate the canals. There is a considerable variation and aberrant root canal anatomy in mandibular premolars that can be difficult to diagnose. Mandibular premolars usually have a single root and single canal, presence of 2 or 3 canals in separate roots is rare. Diagnosis and endodontic treatment of such teeth is challenging. This case report describes three cases of endodontic management of mandibular premolars with 2 and 3 root canals in separate roots. The possibility that there is more than 1 root canal in mandibular premolar teeth must be considered in the radiographic and clinical examination during root canal treatment.