Diego Columbus died in Spain in 1526, but his widow, María Álvarez de Toledo, remained at the palace until her death in 1549.

The palace's Tapestry collection, spanning from the 15th to 17th centuries, is particularly significant and unique in the Caribbean, featuring pieces produced by the Flemish Van Den Hecke family from cartouches created by Charles Le Brun.

[2] The palace was constructed following the design of an existing structure in Mancera de Abajo, in Salamanca, Spain, of which ruins are still preserved.

During the early Spanish colonial period, the mansion played a significant role in history, serving as the base for planning many expeditions of conquest and exploration.

Diego Columbus died in Spain in 1526, but María Álvarez de Toledo, his widow, remained there until her death in 1549.

As the influence of the Captaincy General of Santo Domingo declined, the house deteriorated, and by the mid-18th century, it was abandoned and at risk of decay.

The building now houses the Museo Alcázar de Diego Colón, which exhibits the Caribbean's most important collection of European late medieval and Renaissance art, acquired in the 1950s.