Contemporary patterns of genetic variation in crops reflect historical processes associated with domestication, such as the geographic origin(s) of cultivated populations. Although significant progress has been made in identifying several global centers of domestication, few studies have addressed the issue of multiple origins of cultivated plant populations from different geographic regions within a domestication center. This study investigates the domestication history of jocote (Spondias purpurea), a Mesoamerican cultivated fruit tree. Sequences of the chloroplast spacer trnG-trnS were obtained for cultivated and wild S. purpurea trees, two sympatric taxa (Spondias mombin var. mombin and Spondias radlkoferi), and two outgroups (S. mombin var. globosa and Spondias testudinus). A phylogeographic approach was used and statistically significant associations of clades and geographical location were tested with a nested clade analysis. The sequences confirm that wild populations of S. purpurea are the likely progenitors of cultivated jocote trees. This study provides phylogeographic evidence of multiple domestications of this Mesoamerican cultivated fruit tree. Haplotypes detected in S. purpurea trees form two clusters, each of which includes alleles recovered in both cultivated and wild populations from distinct geographic regions. Cultivated S. purpurea populations have fewer unique trnG-trnS alleles than wild populations; however, five haplotypes were absent in the wild. The presence of unique alleles in cultivation may reflect contemporary extinction of the tropical dry forests of Mesoamerica. These data indicate that some agricultural habitats may be functioning as reservoirs of genetic variation in S. purpurea.