Primary intracranial squamous cell carcinoma is extremely rare, with most cases arising from malignant transformation of dysembryogenetic lesions such as epidermoid and dermoid cysts. Intracranial squamous cell neoplasm arising de novo is even rarer and has been reported in only four patients to date. We herein describe a case of primary intracranial squamous cell carcinoma arising de novo in the right frontal lobe in a 35-year-old woman treated with a combination of surgery and postoperative conformal radiation. We have also shed light on the biology and the therapeutic options of this enigmatic tumour.