Root canal therapy in teeth with root fenestrations can present with pain on apical palpation or persistent pain. The signs and symptoms of root fenestration in the absence of mucosal fenestration may be misleading, which may be misdiagnosed as non-odontogenic pain. Although CBCT is superior to periapical radiographs for the diagnosis of root fenestration, it failed to detect the intact cortical plate in the middle third in our cases. Therefore, the type was different in CBCT from its actual size surgically. Repeated non-surgical root canal treatment would not alleviate pain in the presence of root fenestration and may lead to apical root fracture. Root-resection relieves pain, unless the fenestration is accompanied by fracture. The aim of these two case reports was to describe the diagnosis and treatment of endodontically treated teeth with a persistent pain. Also, the difference of root fenestration type between CBCT and its actual size was described.