Although Entamoeba histolytica is the third leading parasitic cause of death in the world, most infections in humans are asymptomatic and restricted to the intestinal lumen. Entamoeba histolytica infections have also been reported in most species of captive nonhuman primates, with New World monkeys being particularly susceptible to fatal invasive amebiasis. In contrast, Old World monkeys appear to be resistant to the disease, although tissue invasion in asymptomatic monkeys has been reported. Our initial objectives were to determine the incidence, the predisposing factors, and the light microscopic and ultrastructural features of invasive amebiasis in Macaca mulatta (rhesus) and and M. fasicularis (cynomolgus) macaques. Our findings indicate that nonpathogenic E. chattoni in macaques can invade cecal mucosa rapidly (within 1 hr) after death. Therefore, the presence of invasive Entamoeba trophozoites in routinely collected necropsy materials should be interpreted with caution, particularly in cases where tissue fixation is delayed.