Squamous cell carcinoma arising from perineal fistula in patients with Crohn's disease (CD) is a rare entity, with few reported cases in the literature making its clinical characterization troublesome. The outcome is poor following operative treatment as the malignancy of chronic perineal fistula in Crohn's disease is usually overlooked and tardily diagnosed. We present a unique case of a 47-year-old man with a 20-year history of chronic perineal fistula that was diagnosed with extensive perineal squamous cell carcinoma extending down to the right thigh. Computer tomography showed locally advanced disease with inguinal and lung metastasis. Treatment was consisted of diverting colostomy and palliative care. The patient died 3 months later. The clinical data and clinicopathological features of reported cases in the literature were reviewed.