Perineural spread (PNS) of head and neck skin cancer represents advanced stage disease in which tumour spreads along nerves from the site of origin back to the skull base, into the ganglion and ultimately the cisterns and brainstem. Squamous cell carcinoma (SCC) is the most common type, with the typical clinical presentation involving loss of cranial nerve motor function and/or sensory disturbance. The current treatment paradigm for PNS consists of surgical resection and post-operative radiotherapy or radiotherapy alone for advanced disease extending beyond the respective nerve ganglion, however the emergence of immune checkpoint inhibitor (ICI) therapy poses a potential treatment alternative without nerve sacrifice for patients with this disease. This study analysed clinical outcomes at a single tertiary centre of 40 patients over a 5 year period with PNS from cutaneous SCC who received ICI therapy. The overall clinical response rate was 75%. Of the 20 patients with impaired motor function, 12 patients (60%) experienced clinical improvement. This included 9 of 11 (81%) with oculomotor dysfunction and 3 of 10 (30%) with facial nerve palsies. Of the 40 patients, 30 had an overall symptom response. 18 of 21 patients experiencing pain and paraesthesia/dysaesthesia had improvement in symptoms and 12 of 17 patients with a subcutaneous mass experienced a reduction in size. The results suggest functional recovery occurs following commencement of ICI emphasising the need for earlier use of ICI and a subsequent response adapted approach to surgical and radiotherapy management to reduce morbidity.