Hyperthermic isolated limb perfusion (ILP) (2 mg, TNF-alpha and 100mg, melphalan) was performed for an irresectable right thigh desmoid tumor with calf extension in a 49-year-old man. The patient had a history of four resections since the age of 19 years. Local ILP toxicity appeared with extensive edema and common peroneal neurologic impairment including paresis that remained severe 10 months later. One of the most troublesome side effects of perfusion is peripheral nerve damage, which has been reported at a rate of between 1 and 48% of perfused patients. ILP is an effective treatment in recurrence situations or where resection threatens loss of function; it, however, requires administration in specialized centers, progress in standardization and close monitoring to avoid locoregional toxicity, the mechanisms of which merit further investigation. Emergency compartmental pressure measurement may indicate fasciotomy, can be of great interest.