Giant inflammatory pseudopolyps (> 15 mm) are an uncommon complication of inflammatory bowel disease (IBD) and a differential diagnosis with adenomas and carcinomas is challenging. Although usually asymptomatic, they may result in intestinal obstruction or intussusception due to their size. The standard management involves lesion biopsies and endoscopic excision for selected cases; surgery is usually reserved for size-associated complications or an uncertain pathology. We report the case of a 43-year-old female patient with Crohn's disease (CD) in clinical remission, with no specific treatment at the time. A giant pseudopolyp of 40-mm was found during a screening colonoscopy. Therapy was initiated with infliximab and azathioprine in an attempt to reduce the size of the polyp and allow an endoscopic resection. Additional colonoscopies were performed following induction doses at weeks 0, 2, and 6, which revealed a reduced lesion size. Mucosal resection was attempted but failed due to severe fibrosis, which prevented base injections from lifting up the polyp. However, a follow-up colonoscopy three months later showed that the lesion had completely disappeared. The evidence in the literature regarding giant pseudopolyp management is scarce, but reports indicate that they rarely disappear with medical therapy alone and usually require surgery or endoscopic resection.