Giant inflammatory polyps (GIPs) are a rare complication of IBD resulting from chronic regenerative and healing processes leading to a polypoid formation on inflamed mucosa. We reported a case of GIP in a patient with long standing left-sided ulcerative colitis (UC); a well circumscribed sessile GIP was found during a colonoscopy for colorectal cancer screening on a normal colonic mucosa in the cecum. After a severe flare of the left-sided colitis and due to partial response to steroids patient was treated with adalimumab; new colonoscopy after 6 months shows complete disappearance of the GIP previously described. It is the first case report of GIP in normal macroscopic mucosa with complete disappearance after biologic treatment.