ABSTRACTMadelung’s disease is characterised by multiple symmetric abnormal fat masses in the head, neck and upper limbs. Surgical excision or liposuction is the only realistic available option, although palliative in nature. The serial intralipotherapy with phosphatidylcholine/deoxycholate has been proposed as a non-invasive treatment of Madelung’s disease. The authors used serial intralipotherapy with phosphatidylcholine/deoxycholate in two patients affected by Madelung’s disease. Three injections per lesion per patient were performed with 1 month’s interval. Pre- and 6 months’ post-treatment dimensions were assessed with ultrasound scan and patients were observed along a 5 years’ clinical follow-up. A 42.5% average size reduction was reported in all treated lesions. About 33% recurrence rate was observed in the 5 years’ follow-up. We confirm the efficacy of intralipotherapy in the non-invasive palliative treatment of Madelung’s disease, as a valid option to reduce the volume and limit the growth of the pathological adipose masses.