OBJECTIVES:   The aim of this research is to assess biosimilar adoption by the Italian National Healthcare System in 2014 and 2015, analyzing and comparing regional legislative measures and biosimilar penetration, among four therapeutic areas (TNF inhibitors, erythropoietins, granulocyte colony-stimulating factor G-CSF and growth hormones). METHODS:  A desk-based research examined and compared the different regional legislative deliberations on biosimilar. Furthermore, the study was completed with the analysis of molecule consumption at regional level. Consumption data (source IMS Health data) were collected through all the distribution channels of the selected drugs: hospital in-patients distribution, hospital and local healthcare unit direct distribution. RESULTS:   The majority of Italian regions have designed legislative measures to foster the adoption of biosimilars as first choice treatment for naïve patients and, in some cases, to address specific saving objective and consumption target. The analysis of the regional consumption shows important differences in market penetration of biosimilar drugs versus their reference products. Regional penetration ratio ranges from a minimum of 15% (anti TNF drugs, recently introduced into the market) and a maximum of 89% (G-CSF). Finally the study shows a continuous increase of biosimilar adoption, with different growth rate among regions and therapeutic areas. CONCLUSIONS:   Italy lacks of a binding central guide on biosimilar usage, allowing a fragmented regional regulation and penetration. Although there are significant differences among regions, all of them encourage biosimilar uptake by setting switching guidelines, prescribing incentives and tendering schemes. Regional regulation plays a key role in promoting a wider diffusion of biosimilars, bringing relief to limited healthcare budgets.