Received: 27-10-14 Accepted: 06-04-15 Abstract Subepithelial lesions (SE) are rare. They are found in only one out of every 300 endoscopies (0.36%). Of these, only 10% are located in the duodenum. When endoscopy does detect a subepithelial lesion in the duodenum it is important to make an initial description of its size, shape, color, mobility, and consistency to touch. Next, a closed biopsy sample must be taken with pincers and analyzed to detect whether it is a cyst and whether it has a pillow sign which is highly suggestive of lipoma. When the lesion is neither a cyst nor a lipoma, endoscopic ultrasound is indicated, especially if the lesion is larger than one centimeter.