Introduction Graft-versus-host disease (GVHD) and Cytomegalovirus (CMV) infection of the GI tract can occur concomitantly as a complication of allogenic stem cell transplantation (SCT). Repeat endoscopy is sometimes necessary to diagnose GI CMV in the setting of GVHD. Case Patient is a 42 year old female with relapsed acute lymphoblastic leukemia (ALL), s/p chemotherapy and allogenic SCT who presents with intractable diarrhea. Her post SCT course was complicated by recurrent C. difficile diarrhea, CMV viremia and cutaneous GVHD. The Gastroenterology (GI) service was consulted and colonoscopy revealed diffuse colitis with crypt loss and focal apotosis consistent with Grade 2 GVHD. No evidence of infection was seen. She was started on IV steroids and tacrolimus, however, had persistent diarrhea. CT showed non-specific colitis and repeat infectious work-up was unrevealing. GI was re-consulted, and the utility of repeating a colonoscopy in the setting of known GI GVHD was considered. Repeat endoscopy revealed terminal ileum mucosa with extensive ulceration, neutrophilic exudate, apoptosis and regenerative changes suggestive of Grade 4 GVHD (Figure 1 and 2). CMV immunostain was positive, as was CMV PCR (Figure 3). Given findings, she was treated with IV foscarnet with eventual resolution of GI symptoms. Discussion Diagnosis of CMV infection in the setting of GVHD is challenging. After SCT, both are common complications and can occur together. The histologic hallmark of GI GVHD is epithelial cell apotosis. This is however nonspecific as other etiologies such drugs and infections including CMV are known to elicit epithelial apoptosis. During initial colonoscopy in our case, inclusion bodies were not seen, and CMV PCR was negative. Although CMV PCR has a high sensitivity at 89%, it is not perfect, as evidenced by an initially negative result. An important learning point is that repeat endoscopy might be necessary if there is no improvement despite treatment. A similar case is reported by Sun, et. al. Further, GI CMV disease was diagnosed at follow-up endoscopies in 39% of patients with GI GVDH in a study by Cho, et. al. As GI CMV can lead to dire complications such as obstruction and perforation, accurate diagnosis is vital and justifies repeat endoscopy.1914_A Figure 1. Terminal ileum showing ulceration and edema.1914_B Figure 2. Microphotograph of colonic biopsy showing changes of GVHD including apoptosis (arrow), crypt loss (arrowheads) and regenerative changes.1914_C Figure 3. Microphotograph of terminal ileal biopsy showing background of severe GVHD without surviving crypts. Few viral inclusions are seen (arrows) that are positive for CMV with CMV immunostain (dark brown nuclear staining in the inset).