Aim The floristic affinities between Cuba and the Yucatán Peninsula are of great interest for plant geography and preservation of biodiversity in the Caribbean region. Although many authors have stressed the relationship between these regions, the conclusions are based mostly on general descriptive studies. Here we present a quantitative analysis in order to determine their floristic affinities.Location We compared the Mexican portion of the Yucatán Peninsula (states of Campeche, Yucatán and Quintana Roo) and several karst areas of the Cuban Archipelago; which were selected because of the great physiographic, climatic and vegetational similarities.Methods Data obtained from specialized references were used to create a taxonomic data base, this was complemented with a data base (D-BASE) that included data from herbarium specimens. Geographical information was obtained and adapted for use in a numerical taxonomy and multivariate system program (NTSYS). Using the latter, we performed a floristic affinity analysis using a monothetic method based on the comparison of the presence and absence of species. Floristic similarity was obtained using the Jaccard index of similarity and a dendrogram was created.Results Of a total of 1936 species, 880 were common to both Yucatán and Cuba; most being herbaceous species, followed by trees and bushes. The flora of Mexican island of Cozumel exhibited the lowest coefficient of similarity (11%) when compared with the rest of the sites considered. The second level in the dendrogram shows the branching of two large groups: the three states of the Yucatán Peninsula and the coastal areas of Cuba, and the Cuban interior. Highest similarity (73%) within the Cuban areas considered was obtained between the Isla de la Juventud and the Guanahacabibes peninsula; both areas also showed the highest floristic similarity with the Yucatán Peninsula (67%). The Cuban keys and the coastal plain of Tunas form a second group of Cuban localities that exhibited a relatively high floristic affinity with the Yucatán Peninsula. The areas of Maisí, Morrillo and Chico, in east Cuba, form a group with considerably high similarity (50%), and are physically the closest to Yucatán after the Coco–Romano–Caguanes group. The Cuban areas below 600 m in elevation were the least similar to the Yucatán Peninsula.Main conclusions Despite earlier suggestions, there are various areas of Cuba that have close floristic affinity with the Yucatán Peninsula, sometimes based on the presence of specific taxa, and other times based on large groups of taxa common to both study areas with different and broader types of distribution. The number of species (880) common to both the Yucatán Peninsula and the different karst areas of the Cuban Archipielago surpasses all expectations, as the native flora of the Yucatán Peninsula is estimated to have at least 1777 species, and if we exclude exotic, introduced and cultivated species, the general floristic similarity between Cuba and the Peninsula of Yucatán should be about 50%.