Multiple symmetric lipomatosis (MSL), also called Madelung disease, is a disorder characterized by non encapsulated lipomas and fat accumulation around the posterior cervical region and upper trunk. It has been described in patients with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome. We report a 73-year-old woman with MERRF syndrome presenting with MSL. First symptoms consisted of progressive muscular fatigability of lower limbs at the age of 69 years. There was no history of myoclonus, epilepsy or ataxia. Physical examination showed an abnormal fat distribution and giant lipomas of shoulders and neck. There was no amyotrophy and muscular strength of limbs was normal. Serum CK was 207 U/l, lactate 3.2 mmol/l and pyruvate 135 μmol/ l (lactate/pyruvate ratio 23.7). Urinary organic acids were normal. EMG disclosed myopathic changes in the upper limb-girdle muscles. Histology of quadriceps muscle revealed lipid accumulation and ragged-red fibers. Blood DNA analysis identified a heteroplasmic m.8344A>G mutation of the tRNA-lysine gene. Although a rare initial presentation, MERRF should be sought for in all patients with MSL given its potential severity and the implications for genetic counselling. As the mitochondrial content of adipocytes is high, it is thought that the 8344A>G mutation interferes with the maturation of fat cells.