Dendropanax (Araliaceae) is a genus of about 80 species disjunctly distributed in tropical to subtropical Asia and the Neotropics, showing an amphi-Pacific tropical disjunction. The phylogeny of the genus was constructed by sampling 95 accessions representing 33 species of Dendropanax and 43 closely related taxa using sequences of the nuclear ribosomal internal transcribed spacer (ITS) region and six plastid regions (the ndhF gene, the trnL-trnF region, the rps16 intron, the atpB-rbcL intergenic spacer, the rpl16 intron, and the psbA-trnH intergenic spacer). Phylogenetic analyses of the combined plastid and ITS data suggested that the monophyly of Dendropanax was not supported because the Asian D. lancifolius - D. hainanensis clade did not group with the main Dendropanax clade. Nevertheless, the maximally parsimonious trees (MPTs) from the analysis constraining Dendropanax as a monophyletic group were only one step longer than the unconstrained MPTs. The New and Old World Dendropanax species except D. lancifolius and D. hainanensis each formed a robustly supported clade, and the two clades were sister to each other. Based on the biogeographic analyses and fossil-calibrated Bayesian dating, Dendropanax was hypothesized to have originated in the Old World and migrated into the New World via the North Atlantic land bridges in the early Tertiary. The amphi-Pacific intercontinental disjunction of Dendropanax was dated to be 41.83 mya with a 95% high posterior density [HPD] interval of 28.46–56.15 mya.