Irinotecan (CPT-11) is a chemotherapeutic drug used to treat tumors by acting on malignant cells through inhibition of DNA topoisomerase I and inducing premature apoptosis. Major toxic effects of Irinotecan are myelosuppression and gastrointestinal (GI) toxicity, which limits the dose of administration, particularly severe diarrhea with a delay of onset. However, according to the literature, serious GI side effects are uncommon, comprising 3% of the reported cases. The mechanism of Irinotecan-induced delayed diarrhea is unknown and unpredictable. To our knowledge, this is the first case of colitis associated with Irinotecan administration for temporal glioblastoma documented by biopsies. The histopathologic findings are described and the potential mechanisms inducing such lesions are discussed