This article examines the settlement patterns of Preguane and Guane prehispanic cultures in Eastern Colombia. From the results of the archaeological project entitled “Study of the archaeological, geological, environmental and landscape heritage in la Mesa de los Santos: bases for eco-development projects”, we provide an initial approach to explain the differences and similarities of the socio-historical and cultural development in the 11th century in present-day middle eastern Santander, Colombia (South-America). Taking into account the data obtained from the archaeological site of Los Teres, we open a discussion about the existence of two prehispanic communities that inhabited the same territory in different periods of time and were independent in their origins, their historical development and their socio-cultural evolution. Preguane is a prehispanic culture which socio-cultural activity was present until the 11th century in la Mesa de los Santos, and Guane group is a later social phenomenon which origin is still unknown, but which presence was evident in Northeastern Colombia in the 12th century. The differences and similarities in the material culture items are a key to formulate this initial diachronic approach to the socio-cultural sphere of prehispanic eastern Colombia, highlighting the consolidation of processes and realities that are linked with the Republic of Venezuela. This approach is supported in the stratigraphic and cultural context, the spatial distribution (vertical and horizontal) of the pottery and