To report a case of apical fenestration and overfilling in which unusual pain characteristics made differential diagnosis challenging. A 32-year-old woman with diffuse, spontaneous, moderate pain in the maxillary left posterior sector, exacerbated by masticatory and facial muscle movement, with intense sporadic electric-shooting pain, underwent clinical examination and 3D cone beam computed tomography (CBCT). Apical fenestration with protrusion of the mesial root of tooth 26 beyond the buccal cortical plate, extrusion of canal filling material into the soft tissues and a periosteal reaction were detected. Surgery was performed under the operating microscope. The filling material and surrounding fibrous tissue were located, dissected from healthy soft tissues and removed. The mesiobuccal root apex was resected with a bur to within the bony crypt. A root end was prepared and filled with Tech Biosealer RootEnd™ (Isasan, Como, Italy). At the 2-week recall, the patient had complete resolution of the symptoms and good soft-tissue healing. The 1-year recall examination and intra-oral radiography confirmed complete resolution of the symptoms and health of periradicular tissues. Apical fenestration may occur in 9% of cases and may be considered an anatomic predisposing factor for persistent pain after root canal treatment. This complication provides a considerable differential diagnostic challenge and is often misdiagnosed and mistreated. When correctly diagnosed through an accurate, multidisciplinary approach, it may be managed with a simple surgical procedure in which the endodontist should play a key role. Misdiagnosis and over treatment of apical fenestration, through the surgical management of chronic facial pain conditions, could lead to severe exacerbation of chronic pain, which may potentially become persistent or, indeed, intractable.