The prevalence rate of lower gastrointestinal bleeding in patients with AIDS is around 2.6%. A 42-year-old woman with AIDS (CD4 count 9/μL) and recently treated for disseminated histoplasmosis presented to the emergency room with melena, severe anaemia and fever. A colonoscopy showed an umbilicated colonic nodule mimicking a carcinoma of the colon. The biopsy showed intracytoplasmic microorganisms compatible with Histoplasma capsulatum. She had poor compliance to the itraconazole when discharge on previous admission. Despite the fact that colonic histoplasmosis is uncommon, the mortality rate is around 8% and clinicians should be aware of the clinical presentation of histoplasmosis when recur, especially in patients not taking the itraconazole for long-term treatment.