In case of a long-term periapical lesion, destruction of both vestibular and oral cortical plates is sometimes observed and even a through-and-through periapical lesion occurs. The success of the treatment decreases when an apicomarginal defect is added to the through-and-through periapical lesion. Large periapical lesions should be treated initially by orthograde root canal therapy. When the signs and symptoms of the infection don’t recede after the treatment, then surgical approaches should be considered. In this case report, a 22-year-old female with previously initiated therapy was referred for an endodontic microsurgery of tooth 22. After the endodontic treatment the patient was referred to the oral surgeon for apicoectomy with augmentation of the bone defect. The sinus tract in the apex area of the tooth 22 remained active since the surgical intervention. Endodontic microsurgery and guided tissue regeneration were performed. After two-year follow-up, radiographic examination revealed significant bone reconstruction and clinical signs and symptoms were absent. The patient hasn’t reported any symptoms since.