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Background MERRF (Myoclonic Epilepsy with Ragged Red Fibers) is a rare multisystem clinical disorder due to a pathogenic variant of the mitochondrial DNA. Rare symptoms of MERRF include multiple systemic lipomatosis with symmetric uncapsulated lipomas occurs generally on the posterior cervical region and upper back. Methods We report the clinical case of a 46 years-old Caucasian man with MERRF syndrome who presented with MSL on the right cervical region. We decided to perform a mini-invasive approach using laparoscopic instruments. We performed a 10-mm incision about 5 cm under the mass and conducted a blunt dissection of the subcutaneous plane. Then we positioned a 10-mm port and started CO2 insufflation until 10 mmHg to expand the subcutaneous space. During the procedure we setted insuflation to 8 mmHg with the aim to avoid massive subcutaneous emphysema and compression on vascular structures and trachea. We identified the avascular plane between muscular fascia and giant lipoma to perform a blunt sharp dissection. During dissection we identified clear landmarks like pectoralis fascia and sternocleidomastoid muscle. At the end of dissection we morcellated the benign lipomatous lesion for extraction through 10-mm port side. Discussion Video-assisted surgical techniques offer an effective and cosmetically superior approach for excising benign subcutaneous masses. Endoscopic technique has already been adopted in other surgical specialties like pediatric surgery. Conclusion In this case we used laparoscopic standard instruments with CO2 insuflation in order to create a avascular dissection plane and reduce post-operative wound and nerve complications.