Cytomegalovirus (CMV) is a known cause of ulcerative oral lesions among HIV-infected patients, but such ulcers have not been previously reported in recipients of solid organ transplants. We describe a case of a renal transplant recipient who developed severe CMV-associated oral lesions despite prophylaxis with valganciclovir, and in the absence of detectable CMV viremia. The diagnosis was made only after multiple biopsies of the lesions. The patient recovered upon reducing immunosuppression. Potential pitfalls in making a prompt diagnosis are reviewed. The differential diagnosis of a large oral ulceration in a transplant recipient is broad, but should include CMV infection.