The case of a toddler with long-channel cloaca, mild chronic kidney disease (CKD) due to renal dysplasia, and early onset of ulcerative colitis (UC) is herein reported. The patient underwent definitive repair of cloaca, that included vaginal elongation with colon, at 5 months of age and was admitted for episodes of vaginal bleeding at 22 months of age. A vaginoscopy revealed a severe inflammation of the colonic neovagina. As rectal bleeding was also noticed, she underwent a colonscopy that showed the same macroscopic inflammatory picture. Neovaginal and colonic biopsies confirmed UC. The mother turned out to be affected by UC since adolescence. The patient is now on oral therapy with mesalazine and topical steroid and mesalazine in the neovagina. The association between cloaca and inflammatory bowel disease (IBD) is anecdotal, but the family history of IBD should be considered when planning the surgical reconstruction of patients with cloaca. In this patient, the occurrence of UC may require a new neovagina in the future and the concomitance of CKD may complicate the overall management due to the potential nephrotoxicity of drugs used for UC therapy.