This study aims to analyze relationships between large companies and start-ups, in terms of new knowledge exchange. A start-up can have collaborations with large companies in different phases of its life cycle. This study focuses on a firm-level approach that considers new knowledge acquisition from collaborations in different stages of the start-up life cycle. What kind of relationship can influence the development of a start-up? In what way new knowledge acquired may change the start-up performance? The methodological procedures of the research were predominantly qualitative. This paper analyzes a typology of relationships between large companies and start-ups in different phases of their life cycle, examining the role of knowledge management and learning mechanisms in inter-organizational contexts. A questionnaire was distributed to a sample of start-ups. The questionnaire focused on collaborations with large companies and how this collaboration changes knowledge exchange. This paper reports a descriptive analysis of the obtained results. This study focuses on knowledge exchanges in the context of the relationships between large companies and start-ups. This paper examines collaboration in different stages of the start-up life cycle investigating, in particular, how these relationships influence knowledge exchange. Furthermore, the questionnaire allowed to gain information about the start-up and its entrepreneurial network. The analysis allows a deeper understanding of relationships in inter-organizational context on start-ups’ knowledge exchange processes. These results can contribute to the development of tools, indicators and methods aimed to better manage knowledge in new, high-tech firms. Such tools are useful both for entrepreneurs and managers and for consultants. Start-ups should improve their networking attitude and the propensity to meta-goals configuration to sustain long term relationships.