We report the case of a 45-year-old female patient with an 18 month diagnosis of distal ulcerative colitis (proctosigmoiditis) of 18 months, who presented initially with allergy to salicylates, for which the disease was managed with corticosteroids and azathioprine and subsequently with Infliximab infusions, entering in remission. When she was about to receive her fifth Infliximab infusion she presented an exacerbation of her underlying disease with frequent stools with mucus, blood and tenesmus. Given that her initial diagnosis was made with a sigmoidoscopy we scheduled a total colonoscopy showing marked inflammation, erythema and friability limited to the recto-sigmoid mucosa, like at the disease onset, and when we reached the cecum an erythematous area circumscribed to the appendiceal orifice was observed, with a mucosal aspect identical to the described for the recto-sigmoid mucosa. The biopsies taken from that area were compatible with ulcerative colitis. We herein describe the details of the case and review the literature.