Construction of the palace at the site was begun in 1513 under the ownership of Giuliano de' Medici, Duke of Nemours, then captain general of the Roman Catholic church and relative of the pope.

The project was initially conceived by Jacopo Sansovino, including the elegant courtyard with fountains, but work remained incomplete for nearly 70 years, when it was purchased by Ludovico Lante, who completed the structure and whose name is inscribed on the portal.

His son would marry Lucrezia della Rovere, heir of the family of Pope Julius II.

Under the Cardinal Marcello Lante della Rovere the work by Lunghi and Romanelli were completed.

The frescoed lunettes in the piano nobile, depicting episodes and legends from Ancient Roman history, are by Giovanni Francesco Romanelli.