Introduction. Hyperbaric oxygen therapy is known to improve wound healing in the setting of chronic, nonhealing wounds of irradiated skin; however, failure of wound healing may still occur. Dehydrated human amnion/chorion membrane (dHACM) grafting is a technology that has been proven to promote wound healing of wounds related to venous stasis. Little has been published to date regarding use of dHACM in the setting of nonhealing wounds of irradiated skin. Case Report. A 75-year-old man with a history of squamous cell carcinoma of the nose presented to the wound clinic with a chronic, nonhealing nasal wound following tumor resection, radiation therapy, and full-thickness skin graft and auricular cartilage allograft failure. The patient was found to have a nasal cutaneous fistula associated with rhinorrhea, adjacent skin irritation, and discomfort related to the passage of air through the fistulous tract. Following 30 days of standard wound care in the wound clinic (including weekly debridement), the patient continued to have an open, nonhealing wound. As he preferred not to proceed with a surgical flap reconstruction, the patient elected to continue with more conservative management. Hyperbaric oxygen therapy was initiated with some success but with continued presence of a nonhealing fistula tract. A dHACM graft then was applied with successful resolution of the patient’s symptoms and decrease in defect size of 45% after 4 applications. Conclusions. This treatment approach ultimately resulted in complete reepithelization of the wound, and a decrease in defect area. The patient’s symptoms of nasal drainage and physical discomfort due to air passage through the fistula also had resolved completely. Although the fistula was still present at the conclusion of treatment, the tract was well-epithelialized and overall size of the defect diminished greatly.