The aim of the present work is to study the evolution of organizational knowledge within Academic Spin-off (ASO) firms throughout their life cycle. The exploitation of tacit and indivisible new knowledge developed in the context of academic institutions entails agency problems of different nature; one way to address such challenges is the creation of new business firms by the inventors. At the same time to remain viable and competitive the firm will need to either possess or develop a complex mix of tangible and intangible resources. This work studies the process of firm evolution by looking at the governance mechanisms within and across a Regional sample of ASOs throughout the different stages of their development path. While the scholarly literature indicates implicitly that such a path is unique across all firms, our findings identify a high variety of organizational structures evolution paths undertaken by different firms. On these grounds the study offers some reflections in relation to the theory of the firm.