The oldest documentation of milking dates around 7000 years ago in Lybia’s region. The consumption of cow’s milk was possible only in pastoralist populations such as the European, African, and Middle Easterner. The interest of researching indigenous peoples of the Americas arises not only from the fact that they were isolated for thousands of years from populations with a culture of dairy consumption, but also from the demographic relevance (high reproduction rates) of the impact on mixed-race groups with whom they share their gene pool. The genetic trait of lactose intolerance has been attributed to single nucleotide polymorphisms in Europeans and Africans upstream of the lactase gene (LCT). The main objective of this work was to study the molecular variation associated with lactose intolerance in indigenous groups of Lower Central America and appraise their risk of suffering lactose malabsorption. Awareness of lactose intolerance is especially important among these groups due to the potential impact of changes in diet as a result of the increase in acculturation.