Amatus Lusitanus, a Portuguese Jew who gained notoriety as one of the most famous physician-scientists in XVI century Europe published collections of case historiesCenturiaedescribing his most interesting patients. The Renaissance was a transitional period for medicine and the neurological sciences, which if still dominated by the humoral and ventricular-pneumatic doctrines, were taking the first steps away from them. We analysed the Centuriae for neurological and psychiatric cases in order to appreciate neurological practice in this period and selected one hundred which fit those diagnostic categories. The Centuriae contain cases of CNS infection and trauma, epilepsy, apoplexy and depressed states of consciousness (including coma, carus, lethargy and cataphora), headache and vertigo, tumours, cranial nerve paralysis, melancholy, anatomical and physiological observations, as well as a short treatise on cranial traumatology. The most relevant observations point to the importance of the brain parenchyma in cognition, provide original observations of epidemic lethargic encephalitis, describe the neurological consequences of syphilis, including the first description of tertiary syphilis, attempt to distinguish mania from melancholy, extensively describe medical and surgical treatment of cranial trauma, document the first use of anatomical dissection to study a case of brain abscess, negate Galens view of the optic nerves as hollow, and describe the use of new drugs such as guaiac wood for the treatment of headache. The Centuriae not only provide insight into neurological clinical practice in the XVI century, but also emphasize the role of Amatus Lusitanus as an important precursor of this discipline, given his numerous original observations.