AIM: Squamous cell carcinoma developed on a chronic pilonidal cyst. CASE REPORT: Authors describe the case of a squamous cell carcinoma developed on a chronic pilonidal cyst in a 63 years-old patient with a 43 years history of recurrent pilonidal sinus disease. RESULTS: The patient underwent incisional biopsy, staging with total body CT and, finally, radical surgery. After 30 months there were no evidence of recurrence. DISCUSSION: Pilonidal sinus disease is a common disease that affects especially male subjects, obese and with excess of body hair. The complications that arise most frequently are cellulitis, abscess formation and developments of recurrences. Malignant transformation appears rather rare and is reported in the literature with a percentage that goes from 0.02% to 0.1%. CONCLUSIONS: Authors recommend accurate inspection of the pilonidal area in all chronic and longstanding inflammatory lesions and possibly practice incisional biopsies to exclude malignant degeneration.