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BACKGROUND Drug-induced hemolytic anemia is a rare and potentially fatal complication of drug treatment. Specific laboratory tests are crucial to confirm the diagnosis. CASE REPORT A 38-year-old woman on treatment with dimethyl fumarate for multiple sclerosis presented with a 7-day history of weakness and fatigue. Laboratory tests revealed profound hemolytic anemia with hemoglobin levels of 4.7 g/dL (reference, 12.5-16.0), decreased haptoglobin, increased reticulocyte count, and increased indirect bilirubin. A first direct antiglobulin test was negative. The patient was started on prednisone 1 mg/kg/day, and dimethyl fumarate was withdrawn. A blood sample was drawn on Day 7 and sent to a reference laboratory. A direct antiglobulin test performed 7 days later was positive. Furthermore, an indirect antiglobulin test was positive only in the presence of the drug. RESULTS The patient did not receive a blood transfusion, recovered clinically during the following days, and was discharged on Day 7. On Day 36, the patient's RBCs had normalized. She was changed to another disease-modifying treatment for her multiple sclerosis, and at 10-month follow-up she remained stable without any notable adverse effects. CONCLUSION This case describes the first report of a dimethyl fumarate-induced hemolytic anemia. Laboratory results should always be interpreted within the clinical context. Specific laboratory expertise is often needed, given the complexity of the field.