Squamous-cell carcinoma arising in a pilonidal sinus is a rare occasion. Authors report the case of a 60 years old male, with a 15 years history of recurrent pilonidal sinus disease. The patient underwent incisional biopsy, staging with total body CT, and finally radical surgery. The large wound healed by secondary intention, with a complete formation of the scar in three months. After six months, no complications or signs of recurrence were observed. Authors recommend careful inspection of the pilonidal area in all chronic and longstanding inflammatory lesions to identify promptly malignant transformation.