BackgroundWhipple’s disease (WD) is a rare chronic systemic disease caused by the Gram-positive bacillus Tropheryma whipplei. Despite over 100 years of observation and study history of this disease, it still remains a difficult diagnostic and therapeutic challenge.Clinical case presentationAuthors report the case of a 38-year-old man with long-time PPIs treatment because of GERD and no other clinical and paraclinical symptoms. Endoscopic slightly enlarged villi, accumulation of whitish matter at the tip of the villi of distal duodenal mucosa and periodic acid-Schiff staining positive inclusions in the stromal tissue may be typical signs of Whipple’s disease. In discussion the possible explication of this case are presented.ConclusionsIt is still a challenge to diagnose Whipple’s disease. Histological findings may confirm the diagnosis in patients with a combination of typical clinical manifestations, but histological signs alone are not pathognomic, and are not enough for a definitive diagnosis.