Species richness is a fundamental property of biodiversity patterns and is properly expressed by the species–area relationship (SAR), namely the increase in the number of species with the area. Here, we studied and explored the species–area relationship with respect to vascular plant species in Italy and compared vascular plant richness among Italian administrative regions. Concerning the entire vascular flora (native and alien), the best-performing formula is the Arrhenius’ Power function: S = c Az. The constants of this function are c = 241.2 and z = 0.281. The best-performing formula concerning just native (c = 245.2 and z = 0.263) and alien (c = 10.1 and z = 0.404) richness is the Power function as well. The floristically richest Italian regions considering the entire flora are Liguria, Friuli Venezia Giulia, and Trentino-Alto Adige, which are also the regions that are richest in alien flora unfortunately. Regions of particular naturalistic interest are Abruzzo, Valle d’Aosta, and Molise, because only these three regions exhibit native floristic richness that is higher than expected, and this is coupled with an alien floristic richness that is lower than expected. On the contrary, four regions (Lombardia, Veneto, Toscana, and Emilia-Romagna) show potentially severe conservation problems due to biological invasions since they experience native floristic richness that is lower than expected, with an alien floristic richness that is higher than expected. This study offers for the first time the ‘c’ and ‘z’ constants specifically calibrated at the national level for Italian vascular flora. The availability of such constants allows the calculation of the number of expected species for a given area to be investigated, providing a robust starting hypothesis for floristic studies.