Endodontic perforations are common accidents that occasionally happen as a result of misuse or difficult anatomy of some teeth; it may lead to teeth loss unless a good management is provided. Bioceramic (silicate-based) cements like mineral trioxide aggregate have a big role in management of such accidents. This case report aimed to evaluate the ability of five mineral oxides cement “5MO” in sealing two root canal perforations (furcation and postdrill perforations) and inducing clinical and radiographic healing in the periodontal tissues with/without the use of collagen sponge matrix. A 58-year-old healthy female was referred to our dental office complaining of severe pain in the upper left premolars’ region. Periapical radiographic examination revealed unsatisfactory root canal treatment of the teeth #24 and #25 with a furcation perforation and a postdrill perforation, respectively. Cone-beam computed tomography “CBCT” scans confirmed the findings of the periapical radiography and revealed the presence of radiolucent lesions surrounding the apex of both teeth #24 and #25. The treatment plan was a nonsurgical root canal retreatment by endodontic access through the full-ceramic crowns. After three years of follow-up, CBCT scans revealed a complete healing and bone formation on both premolars. This case report indicates the use of 5MO cement for endodontic perforations management.