ELISA was used to test the presence of the human pathogenic amoeba Entamoeba histolytica in archaeological samples from 2 cemeteries in Guadeloupe, in the Caribbean. Results show that 15.9% of the population was infected during the colonial period, a value comparable to the current rates observed in humans in adjacent countries. This study also confirms the presence of the current strain of E. histolytica in pre-Columbian South America before the European colonization in the 15th century and raises the possibility of an earlier transfer from Europe to the Americas.