The corpus callosum can reveal a "butterfly" pattern on imaging in various conditions, including glioblastoma, primary central nervous system lymphoma, tumefactive multiple sclerosis, and toxoplasmosis. Early differentiation among these conditions is crucial to avoid aggressive treatments. In one case, a 70-year-old woman with a history of multiple sclerosis experienced a neurological decline. While imaging suggested a high-grade glioma, a biopsy ultimately confirmed the diagnosis of tumefactive multiple sclerosis. The patient showed improvement with steroid therapy. It is essential to distinguish between high-grade gliomas and tumefactive multiple sclerosis, as gliomas typically present acutely while tumefactive multiple sclerosis progresses more slowly. Utilizing advanced imaging techniques and biopsy aids in achieving an accurate diagnosis, thus preventing unnecessary interventions. Additionally, a multidisciplinary approach is vital for optimal management of these conditions.