OBJECTIVES: Histologic findings after endoscopic resection using submucosal lifting agents Eleview and ORISE gel are described. METHODS: Four cases were identified based on the histologic presence of ORISE gel. Cases were selected to illustrate the histologic appearance of the lifting agent immediately after injection (day 0) and after an interval of approximately 2 months. RESULTS: Immediately after injection, the gel had an appearance similar to acellular mucin on H&E stain and showed mucicarmine positivity but was negative for periodic acid-Schiff stain and Alcian blue. At 2 months, the appearance changed drastically and was characterized by a hard, homogenous eosinophilic quality and elicited a robust foreign body-type giant cell reaction; we have proposed the name lifting agent granuloma for this histologic appearance. The aged material may be mistaken for amyloid or a pulse (legume) granuloma; however, the material was negative on Congo red stain and had a different clinical history and distribution in the tissue from those of a pulse granuloma. CONCLUSIONS: It is important to take note of the histologic appearance of these new submucosal lifting agents over a varying time interval, as outlined here, so that they are readily recognized and not mistaken for other entities.