A woman in her 40s was admitted to hospital with weight loss, asthenia, persistent abdominal pain and post-prandial nausea and vomiting. Other comorbidities were anxiety-depressive disorder, gastro-oesophageal reflux disease and fibrocystic mastopathy. On admission her body mass index (BMI) was 15.57 kg/m²with a reported weight loss of 6 kg during the last 3 months. The patient underwent a double contrast abdominal CT scan, which showed that the third portion of the duodenum appeared to be compressed between the superior mesenteric artery and the abdominal aorta. After a multidisciplinary evaluation, a conservative approach and nutritional supplementation was decided upon and administered. At the 1-year follow-up the symptoms had greatly improved; the epigastric pain, although persistent, was reduced, also due to the weight gain to 50 kg (BMI 19.5 kg/m²). Wilkie’s syndrome, in its acquired form, predominantly affects young women after rapid weight loss. In the diagnostic work-up, case history, physical examination and radiological findings play a key role.