Constructed in the first decade of the 17th century for Cardinal Camillo Borghese, this building came to be called the "Borghese Harpsichord" on account of its unusual shape, similar to the antique musical instrument. The façade which looks onto the Lungotevere, the embankment of the Tiber River, is called the keyboard because of the two rows of loggias, one upon the other.

At the time of construction this part of the river was a busy port, alive with activity.
The Palazzo Borghese, the tallest and most imposing building of its time, was a sure sign of the family's newly acquired economic power. Originally from Siena, their power was ensured when Camillo Borghese became Pope, taking the name Paul V.
A rigorous and uncompromising man, as pope he dispensed enormous privileges to his family members, in particular to his favorite nephew, Cardinal Scipione.
The modest origins of the family can be understood from their surname, Borghese, but their ascent in Rome was rapid and they became one of the city's most powerful families.