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Abstract Background Compression of the median nerve by a tumour in the elbow and forearm region is rare. We present a case of neuropathy of the median nerve secondary to compression by giant lipoma in the proximal forearm. Case presentation A 46-year-old man presented with a six month history of gradually worsening numbness and paresthesia on the palmar aspect of the left thumb and thenar eminence. Clinical examination reveals a hypoaesthesia in the median nerve area of the left index and thumb compared to the contralateral side. Electromyography showed prolonged sensory latency in the distribution of the median nerve corresponding to compression in the region of the pronator teres (pronator syndrome). Radiological investigations were initially reported as normal. Conservative treatment for one month did not result in any improvement. Surgical exploration was performed and a large intermuscular lipoma enveloped the median nerve was found. A complete excision of the tumour was performed. Postoperative revaluation the X-ray of the elbow was seen to demonstrate a well-circumscribed mass in the anterior aspect of the proximal forearm. At follow-up, 14 months after surgery, the patient noted complete return of the sensation and resolution of the paresthesia. Conclusion In case of atypical findings or non frequent localization of nerve compression, clinically interpreted as an idiopathic compression, it is recommended to make a pre-operative complementary Ultrasound or MRI study.