In their daily clinical practice, physicians have to confront diagnostic dilemmas which cannot be resolved by the application of only one imaging technique. In this case report, we present a 66-year-old woman who was admitted to our institution for the surgical resection of a recently diagnosed brain tumor. The patient had a history of epileptic seizures and was hospitalized in the past for anti-phospholipid syndrome related to a non-Hodgkin lymphoma in remission. Magnetic resonance imaging (MRI) examination revealed an enhancing right parasagittal lesion with significant edema suggestive of a high grade glioma. Advanced MRI techniques including proton magnetic resonance spectroscopy (1H-MRS) showed findings compatible of glioma. An additional examination was performed as part of a protocol that we are routinely performing in our institution for all brain tumors including not only the gold standard advanced MRI techniques but also single-photon emission computed tomography (SPECT) with technetium-99m (Tc99m). Brain SPECT indicated the presence of a meningioma which was verified by the histopathology of the resected specimen. In conclusion, a multimodality approach for the pre-surgical assessment of brain tumors has significant advantages not only for the diagnosis but also for the evaluation of intracranial tumors histology.