Mucinous adenocarcinoma (MC) is a unique pathological type of colorectal cancer (CRC). The development of MC is often associated with intestinal inflammation and/or microsatellite instability (MSI). Moreover, MC has clinicopathological characteristics that render making the correct diagnosis difficult such as extramural progression. Meanwhile, intestinal spirochetosis (IS) is a condition in which colonic epithelial cells are colonized and/or infected by spirochetes. Intestinal inflammation due to IS occurs by the destruction of colonic microvilli and induces chronic diarrhea. Recently, it was reported that the prevalence of IS tended to be high in patients with sessile serrated adenomas/polyps, the precursor of MSI-high CRC including MC. This study presents a case of MC in the setting of intestinal inflammation due to IS and tries to clarify the cause of MC development by performing immunohistochemical stain of resected specimen for DNA mismatch repair (MMR) proteins. This patient is a 63-year-old man with no symptoms who had a positive fecal occult blood test. Subsequent endoscopic findings and biopsy results revealed intestinal stricture of the transverse colon and chronic infective colitis associated with IS. Metronidazole therapy was initiated but was not effective. Although follow-up colonoscopy was performed repeatedly, intestinal perforation occurred 20 months later. Subtotal colectomy and ileostomy were performed. Pathological examination of resected specimens revealed MC with normal expression of MMR proteins, including MLH1, MSH2, MSH6, and PMS2. The histopathological classification was Union for International Cancer Control (UICC) IIIB and adjuvant chemotherapy was initiated. This is an interesting case of MC developing in the setting of chronic colitis associated with IS. It seemed that the cause of MC development was not MSI but intestinal inflammation. Besides, endoscopic diagnosis of MC in this case was difficult because of the extramural progression and lack of obvious atypical colonic glands in biopsy specimens. This report provides evidence for an association between neoplasm and IS-induced intestinal inflammation. Moreover, we suggest that making the diagnosis of MC could be difficult because of its unique clinicopathological characteristics.