The aim of this pilot study was to investigate the effects of levetiracetam monotherapy on seizure control, quality of life and neurocognitive performance in patients with brain tumor-related epilepsy. We present here preliminary data from 18 patients with follow-up of 6 months. We evaluated seizure frequency at baseline. We used administered Mini Mental State Examination (MMSE), Karnofsky Performance Status (KPS), Barthel index (BI), QOLIE 31P (V2), EORTC QLQ-C30 and Adverse Events Profile. After 6 months, 16 patients were seizure free (88.9%), 2 (11.1%) had reduction in seizure frequency >50%. Compared to baseline, we observed a worsening of performance (KPS p = 0.011; BI = 0.008) and global lower cognitive performance (MMSE p = 0.011); distress related to seizure frequency (p = 0.003) and medication effects (p = 0.046) were significantly lower. Levetiracetam caused mild and reversible side effects. These preliminary data on LEV monotherapy in patients with brain tumor-related epilepsy show that this antiepileptic drug is efficacious and well tolerated.