Universities are presently considered vital players in the transfer of knowledge, innovation and technology to the economy. This is one of the roots of the diffuse reform processes evident in most European tertiary sectors. In almost 25 years Italian universities have experienced many changes that deeply reshaped their academic institutions. Among other aspects, the need to make an adequate contribution in answer to the demands of society led to an extension and deepening of universities’ so-called Fourth Mission (Geiger, 2006; Kretz & Sá, 2013). A multifaceted set of activities were therefore introduced to strengthen the liaison between academia and society. In the past, this role was mainly concerned with granting patents to outsiders, but today universities are also increasingly dedicated to the creation and promotion of spin-off activities. These are instruments designed to respond to social pressures towards accountability and establish a dialogue with the economy through the sharing of academic research findings. In this framework, the main features of each academic institution are an important variable in the spin-offs’ development process. Through the use of 4 case studies (University of Messina; Polytechnic of Turin; Scuola Superiore Sant’Anna of Pisa; University of Trento) and the analysis of 40 qualitative interviews with key actors in each spin-off (directly and indirectly involved in the entrepreneurial projects), the paper investigates university spin-offs in Italy from two different perspectives. First, the growing number of spin-offs as related to the present conditions of young Italian academic researchers (increasingly affected by budget constraints), university policies, and new management issues. Second, the identity and self-perception of academic actors involved in the spin-offs’ creative process.