Cytomegalovirus (CMV)-associated esophageal ulcer is rare in immunocompetent infants. The presence of inclusion bodies and immunohistochemical staining for CMV in biopsy specimens obtained during esophagogastroduodenoscopy (EGD) indicate that such ulcers occur because of CMV infection. A 7-week-old female infant who experienced frequent vomiting and feeding intolerance was diagnosed with a massive CMV-associated ulcer in the distal esophagus. The ulcer improved after conservative treatment using proton-pump inhibitors; however, ganciclovir was not administered. In a follow-up EGD biopsy specimen, no CMV inclusion bodies were present, and immunohistochemical staining results for this virus were negative. The presence of CMV inclusion bodies indicates active viral replication. If persistent inclusion bodies or positive immunohistochemical staining for CMV is observed in follow-up biopsy specimens, ganciclovir may be used to treat CMV-associated esophageal ulcers.