This review addresses, in a critical historical perspective, the link between seizures and endocranic neoplasms. Folkloric descriptions of epilepsy can be found in writings from ancient cultures. Hippocrates first provided a medical interpretation. In 1770, Tissot published Traité de l’épilepsie, a milestone in epileptology, whereas the 19th century is considered the golden era of epileptic studies. In 1882, the father of modern epileptology, Jackson, in his article Localized Convulsions from Tumour of the Brain, reported a case of a patient affected by typical Jacksonian seizures in the presence of a brain tumor. However, he did not establish a direct correlation between brain tumors and epilepsy, and an explanation for his clinical case was lacking. Before Jackson’s article, other authors reported similar cases, but only Gairdner in 1834 published a report suggesting the concept of a direct relationship between epilepsy and a brain tumor. From the beginning until the mid of the 20th century several authors reported seizures attributed to intracranial tumors, and in recent years studies have focused on the pathogenesis of tumor-related seizures. Biochemical and molecular changes in brain tumors and their environment opened unprecedented working hypotheses on epileptogenesis and on treatment of epilepsy associated with brain tumors.