The induction of autoimmune hemolysis is a rare side effect of oxaliplatin. A 68-year-old patient was referred to our hospital because of progedient jaundice and exertional dyspnea. One day before she had received the 5th consecutive week of treatment of the 8th cycle of a chemotherapy according to FUFOX protocol with oxaliplatin and 5-fluorouracil because of metastasized adenocarcinoma of the sigma. Laboratory values revealed hemolytic anemia associated with thrombocytopenia and neutropenia. In the further clinical course a rapid decline of the hemoglobin (hb) level could be observed associated with a significant increase of hemolysis parameters. A direct Coombs test was positive consistent with oxaliplatin-mediated autoimmune anemia (AIHA) and a pulse therapy with steroids was started accompanied by transfusions resulting in a normalization of red blood cell and white blood cell counts. Chemotherapy was switched to an oxaliplatin-free regimen because of progressive tumor disease and induction of immune pancytopenia. Oxaliplatin-induced AIHA requires an immediate diagnosis since reexposition results in a more severe hemolysis. The direct Coomb's test represents the essential hallmark of the diagnosis.