This case describes our use of longitudinal analysis to examine the career trajectories of Italian regional chief executives. Our research focused on regional chief executives, under the premise that they are neglected actors in comparative studies, despite their growing political relevance. We used Italy as a case study to test two expectations and provide insights for comparative conclusions. Empirical information was based on a unique dataset on Italian chief executives’ socio-demographic background and political experience from 1970 (when Italian regions were established) and 2015. Two hypotheses about the impact of institutional settings and state organization were derived from comparative literature. Italy was selected as a quasi-experimental case study, where there were variations of the conditions of interest within the same national context. The large-N dataset (242 chief executives’ terms in office were the units of analysis) provided aggregate percentages of individuals with specific career backgrounds, whose association with changing institutional conditions was tested through statistical analysis. We describe how we collected and organized data based on theoretical conjectures derived from the literature. Moreover, we show how findings about under-studied topics can be fruitfully understood to develop generalizable knowledge.