This study explores the feasibility of using combined strontium (87Sr/86Sr) and oxygen (δ18O) isotope analyses of archaeological animal remains from Puerto Rico to investigate precolonial networks of exchange in the Circum-Caribbean. Culturally modified teeth (pendants) of animals including jaguar (Panthera onca), peccary (Tayassu pecari), and tapir (Tapirus terrestris) none of which is native to the Antilles were analyzed to investigate their geographic origins. The strontium isotope results were compared to extant databases and spatial models of biosphere 87Sr/86Sr variation for the Circum-Caribbean. The oxygen isotope results were compared to available bioapatite (δ18Oap) and precipitation (δ18Oprec) data sets. Although it is not possible to pinpoint a specific origin based on the isotope data alone, based on comparative analyses from various mainland areas, we tentatively propose that: the two jaguar teeth have clearly distinct origins, with one possibly originating from the Guiana Shield Region of northeastern South America and the other possibly from the Southern Lowlands of Mesoamerica, Central America, or northwestern South America; and that the peccary and tapir teeth have similar isotope values and both may have originated from northern coastal South America, the Metamorphic Province of northern Central America, or the Maya Mountains of Belize. These results indicate that the modified teeth of different mainland species were widely circulated amongst the indigenous societies of the Neotropics, with some objects apparently being transported over a thousand kilometers from the source area to the location of final deposition. The diverse origins of these artifacts support the proposition that objects with distant origins were highly valued by precolonial Caribbean peoples, including the tooth pendants of exotic mainland fauna.