This paper analyses and discusses the patenting activity of Public Research Organizations (PROs) in Southern European countries. Despite the importance of the topic, studies about the European experience are rare. By using an original database of "American" (USPTO) and "European" (EPO) patents held by PROs in Portugal, Spain, France, Italy and Greece, we observe that the number of university patents in these countries has not increased dramatically during the last years, despite a growing interest at both European and national level during the same period. However, differences do exist among countries in terms of number of granted patents and regulative frameworks. With regard to PROs patenting strategies, we argue that PROs should be progressively able to adopt a "balanced" approach, in order to achieve co-existence between the traditional mechanisms of the so-called "open research system" and the more recent concerns about intellectual property protection, technology transfer and regional development.