A 63-year-old man with a history of malignant melanoma was admitted with a 4-day history of severe watery diarrhea, tenesmus, and abdominal pain. Prior to this hospitalization, he had undergone a surgical resection of a stage IIIB melanoma of the anterior abdominal wall followed by treatment with two doses of ipilimumab, a monoclonal antibody directed against cytotoxic T lymphocytes, for his melanoma, with the last dose 7 weeks prior to the current hospitalization. He had had a recent admission for bacterial multi-lobar pneumonia complicated by severe Clostridium difficile infection that was still in treatment with a tapering course of oral vancomycin after completing the antibiotic treatment for pneumonia. Physical examination revealed heart rate of 101, blood pressure of 72/46 mmHg, temperature 38.2 °C, respiratory rate of 18/min, dry mucous membranes, and diffuse abdominal tenderness and some guarding without rebound tenderness. Complete blood count, liver function tests, serum amylase, and serum lipase were all normal. Kidney function tests and fractional urinary excretion of sodium suggested the presence of pre-renal azotemia. After admission, he was intravenously hydrated while the etiology of his diarrhea was investigated with stool microscopic examination, culture, and polymerase chain reaction for C. difficile, which were all negative, diminishing the likelihood of an infectious etiology. An abdominal computed tomography (CT) scan was reported as showing diffuse colonic wall thickening and a number of colonic microperforations consistent with severe colitis (Fig. 1). Due to the severity of these findings, colonoscopy was not performed. The patient was initially diagnosed with an immune-related colitis, possibly due to ipilimumab. Accordingly, ipilimumab was discontinued in favor of IV steroid treatment, which partially improved his symptoms after a week of therapy. Infliximab was then added, with which complete symptom resolution. He was discharged home 2 weeks after admission.