The biogeographic history of southern South America has led to a markedly distinct flora within the frame of the Neotropics, which is also particularly heterogeneous in terms of its eco-geographic distribution. This environmental complexity is at the base of the many and controversial classification systems that have been proposed for the vegetation of the so-called Cono Sur region (Paraguay, Chile, Argentina, Uruguay and parts of Brazil and Bolivia). In this study, we aimed to assess the floristic consistency of the main vegetation types that inhabit the region. Our dataset consisted of 116,130 occurrence records of 3662 species of shrubs and trees in 781 sampling sites spread over six countries and eight phytogeographic domains: Atlantic Forest, Pampa, Gran Chaco, Patagonia, Southern Andean, Mediterranean Chile, Temperate Pacific, and Pacific Islands. We performed a cluster analysis and nonmetric multidimensional scaling ordination analysis of this dataset followed by multi-response permutation procedures and permutational multivariate analysis of variance and taxonomic distinction index and indicator species. The greater differentiation took place among the phytogeographic domains and leaf flush regimes (evergreen, deciduous, and semideciduous) though there was also a remarkable latitudinal gradient. Our analyses showed that the pre-defined vegetation types were consistent in terms of woody flora composition and have a considerable number of indicators, many of which endemic. In terms of conservation prioritization, Atlantic Rain Forest therefore has importance because of its high species richness while temperate and mediterranean forests west of the Andes should not be ignored given that they show much higher endemism than would be expected given their species richness.