Background: Nervous central system metastases from head and neck squamous cell carcinoma (SCC) are rare. We report an exceptional case of isolated leptomeningeal and spinal cord involvement few years after the diagnosis of invasive SCC of the lip. Case Report: A 33-year-old man with a history of infracentimetric carcinoma of the lip developed back pain associated with progressive neurological disorders leading to paraplegia. This atypical presentation led to initial misdiagnosis, but radiological and cytological explorations finally confirmed the diagnosis of leptomeningeal and intramedullar secondary spinal cord lesions from his previously treated head and neck SCC. Systemic targeted therapy with epidermal growth factor receptor inhibitor and intrathecal chemotherapy led to prolonged disease stabilization. Conclusion: To our knowledge, this is the first case of isolated neurological metastases from a head and neck SCC. Combination of systemic targeted therapy and intrathecal chemotherapy may be effective in such cases.