Opportunistic gastrointestinal infections are common in patients with HIV infection; both amebic colitis and cytomegalovirus (CMV) colitis are common causes of chronic diarrhea. It is difficult to distinguish these 2 diseases by nonspecific clinical symptoms such as diarrhea, abdominal pain, and weight loss. Here we report a case of CMV colitis mimicking amebic colitis with elevated indirect hemagglutination assay antibody titer against Entamoeba histolytica and negative IgM antibody titer against CMV. The diagnosis of CMV colitis was confirmed by eosinophilic nucleoli and inclusion bodies in colon biopsies. The patient recovered after ganciclovir and highly active antiretroviral therapy. Exact diagnoses are important for treating opportunistic infections. Other pathogens should be considered in patients with chronic diarrhea who are refractory to initial treatments. Our case highlights the importance of histopathological diagnosis for chronic diarrhea in patients with HIV infection and the possibility of false-positive results for indirect hemagglutination assay antibody against Entamoeba histolytica despite high titers.