This is a unique museum for its subject area, and its origins date back to the Natural History Cabinet created by King Carlos III and to 18th century scientific expeditions.

It boasts pre-Columbian, ethnographic and colonial pieces. Highlights include the Quimbayas treasure, the cloak of a Paracas tribe mummy dating back some two thousand years, the Trocortesiano (Mayan) and Tudela (Aztec) codices, a collection of Inca art, indigenous collections from the north-east coast of the United States and Canada compiled in the 18th century, "plumaria" pieces and "mestizo" paintings.

The exhibition is divided into five subject areas illustrating The Instruments for Knowledge of the Americas, Cultural Areas, Society, Religion and Communication in the Americas.