Ennio De Renzi (1924-2014), physician and neurologist, is the founder of modern Italian neuropsychology. De Renzi not only made important studies, but also formulated methodological principles, overcoming the insufficiencies of the traditional qualitative clinical method of observing individual patients with apparent deficits: research is to be made in groups of patients; the exam is standardized; the patients’ performances are to be compared with those of a group of healthy participants, using statistical methods. This approach, still used for «group» studies, assigns a minor role to «single case» studies, which, however, may be also performed in accord with De Renzi’s recommendations, and have provided, and still provide, a relevant contribution to the understanding of the functional architecture of cognitive processes and of their neural basis.