The upper gastrointestinal tract is not generally considered a target organ in ulcerative colitis (UC). However, several cases showing upper gastrointestinal involvement in UC have been reported. In this report, we present 2 rare cases of diffuse duodenitis accompanying pancolonic UC. Case patient 1 was a 44-year-old man who developed diffuse duodenitis shortly after colectomy and was successfully treated with mesalazine. Case patient 2 was a 25-year-old woman who developed diffuse duodenitis under a steroid-free condition and was successfully treated with prednisolone. The 2 patients had Helicobacter pylori-negative duodenitis that resembled colonic lesions of UC in both the endoscopic and histological findings. No evidence of Crohn's disease was found in these cases. We diagnosed both cases as typical UC-associated diffuse duodenitis. The occurrence of gastrointestinal involvement in UC has been attracting attention because such lesions could potentially open a new window for studying the etiology and pathogenesis of UC. Further studies involving a large number of patients are needed to clarify whether the upper gastrointestinal tract is a target organ in UC.