Cytomegalovirus (CMV) is the leading cause of viral-associated congenital infections. Moreover, it can also be acquired. Between 50 to 80 percent of the world’s population is seropositive for CMV and most clinical disease occurs in individuals previously infected with CMV. Rarely, serious CMV infection has occurred in individuals with healthy immune system. In contrast to immunocompetent patients, higher morbidity and mortality of CMV end organ disease is considered in immunocompromised patients. According to available evidence, gastrointestinal (GI) disease has lower prevalence in case of CMV-induced organ involvement, especially in pediatric non-transplant acute leukemia. In this report, we present a 12-year-old girl, known case of acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy with manifestations of gastroenteritis and significant weight loss. Initial laboratory data, demonstrated mild pancytopenia especially lymphopenia and thrombocytopenia. After excluding more common etiologies, colonoscopy with multiple biopsies were taken which was indicative of CMV-colitis. Intravenous (IV) ganciclovir for 3 weeks and oral valganciclovir for about 9 months were initiated. Follow-up courses for CMV surveillance included blood qualitative CMV polymerase chain reaction (PCR) and colonoscopy with biopsy which were negative for CMV but tissue qualitative CMV PCR was positive for CMV in about 7 months after initiation of treatment. Oral treatment was decided to be continued. To sum up, plenty of guidelines have been developed in stem cell transplantation and human immunodeficiency virus (HIV) patients but non-transplant leukemic setting, is a neglected area in the field of CMV infection management.