Using the Acalyphoideae, we explore the origin and diversification of the Caribbean flora. This lineage of flowering plants constitutes an important component of the flora of the Caribbean islands with many endemics. Furthermore, because it is also diverse in adjacent Mexico, Mesoamerica and South America, it allows a representative analysis of possible migration routes into the Caribbean.Neotropics, Cuba, Hispaniola and the Caribbean region, Mexico and Mesoamerica.We generated a well-resolved and dated phylogenetic hypothesis based on a dense sampling, in particular of the New World taxa but also representing all remaining Acalyphoideae, and combined datasets of chloroplast spacers and introns. Bayesian divergence-time estimation was applied to determine node ages. Ancestral states of distributional areas were reconstructed in a Bayesian framework to determine the geographical origin of the Caribbean ancestors.A Neotropical clade started to diversify 59.29 [50.41–68.44 95% highest posterior density (HPD)] Ma within the Acalyphoideae. The Caribbean islands then were reached several times independently from the Miocene onwards. The exclusively Caribbean Leucocroton–Lasiocroton–Garciadelia [9.1 (6.3–12.3 95% HPD) Ma] and Acidoton–Platygyna [9.3 (5.2–15.4 95% HPD) Ma] clades exhibit one of the most successful plant radiations in the region, and Caribbean subclades of Acalypha and Bernardia just date back to the Pliocene and Pleistocene, respectively.Our data show that Mexico and Mesoamerica have played a key role as a source for today's Caribbean Acalyphoideae. Their ancestors arrived from the mainland to the Caribbean islands during the Miocene when Caribbean land masses were completely separated and then diversified in situ. We postulate long-distance dispersal to have played a major role for colonizing the Caribbean.