Corallus enydris (Serpentes: Boidae: Boinae) is an arboreal snake with an extremely wide mainland distribution from southern Costa Rica to southeastern Brazil and is one of two home species that has invaded the Lesser Antilles (Grenada Bank and St. Vincent). Mitochondrial DNA sequences of samples from seven geographically disparate localities provided evidence of phylogenetic relationships. The monophyly of C. enydris is corroborated and a major dichotomy between northern samples (Panama and Trinidad) and southern samples (Guyana, Perú, southeastern Brazil) was found and corresponds to the two currently recognized subspecies. Unexpectedly, the two samples from the West Indies (southern Lesser Antilles) cluster with the southern rather than the geographically closer northern samples (e.g., Trinidad). The results imply a fairly recent Guianan–Amazonian origin of West Indian populations.