Our aim was to determine whether histological changes occur in the cutaneous portion of pectoralis major flaps employed for upper aero-digestive tract reconstruction and, if present, to characterize these changes and try to infer their cause. Seven patients submitted to repair of aero-digestive tract defects secondary to cancer resection with pectoralis major myocutaneous flap were included in this study. All patients received adjuvant radiotherapy. Biopsies were taken from: the cutaneous portion of the flap; buccal mucosa; irradiated neck skin and chest skin opposite the donor site. Histological changes toward a “mucosalization” occur in the cutaneous portion of the pectoralis major flaps, characterized by disappearance of the horny layer or a reduction of its thickness and a decrease of the amount of cutaneous appendages. These changes are probably a result of continuous exposure to the intraoral environment in association with radiotherapy effects and may represent an advantageous adaptation for the patient.