Abstract Trigeminal trophic syndrome (TTS) is a rare condition in which patients induce unilateral facial ulceration by persistent physical manipulation. Peripheral or central damage to the trigeminal nerve causes anaesthesia, paraesthesia, formication or pruritus. Compulsive skin picking leads to ulceration of the ala nasi, cheek, scalp or mouth in the distribution of the trigeminal nerve. Patients with TTS are often subjected to extensive investigations and can be misdiagnosed as having a psychocutaneous disorder, such as dermatitis artefacta, skin-picking disorder or delusional parasitosis. We describe a 90-year-old woman who developed TTS following rhizotomy and radiofrequency treatment for trigeminal neuralgia. Underlying infectious, malignant and vasculitic causes for her ala nasi and cheek ulceration were ruled out through six incisional biopsies and two punch biopsies over 8 years. Previous treatment of TTS has included patient education and physical barriers (e.g. face masks and occlusive dressings). Treatment to date has been challenging, with trials of medications to address paraesthesia, including carbamazepine, gabapentin and amitriptyline. This patient re-presented to dermatology in 2022 with significantly worsened ulceration to her cheek and severe loss of nasal cartilage. In September 2022, the patient was started on N-acetylcysteine (NAC) 600 mg twice daily, and within 3 months, there was a considerable improvement. This drug is a mucolytic that has historically been used as an antidote for paracetamol overdose. It has antioxidant properties by replenishing glutathione and maintaining redox balance within cells. It also modulates neurotransmitters and can increase glutamate and alter dopamine levels. In addition, it has anti-inflammatory action by inhibiting interleukins (ILs), including IL-6 (Adil M, Amin SS. N-acetylcysteine in dermatology. Indian J Dermatol Venereol Leprol 2018; 84:652). In recent years, NAC has been reported to be successful in small case series and case reports among patients with trichotillomania, skin-picking disorders, onychotillomania, toxic epidermal necrolysis, alopecia, contact dermatitis, atopic dermatitis and wound healing (Grant JE, Chamberlain SR, Redden SA, Leppink EW. N-Acetylcysteine in the treatment of excoriation disorder. JAMA Psychiatry 2016; 73:490). It is an inexpensive drug that appears to be well tolerated and effective. To our knowledge, this is the first case report of the use of NAC in TTS. In summary, this was a case of TTS in a 90-year-old woman who successfully responded to NAC. The drug has antioxidant, anti-inflammatory and neurotransmitter modulatory effects. Reliable randomized controlled studies are needed to confirm the efficacy and optimum dose of NAC. Increased awareness of this rare syndrome and potential treatment options will ensure prompt diagnosis and prevention of permanent disfiguration.