What was supposed to have been a short sojourn in Milan soon became a permanent one. The Florentine government insistently exhorted Leonardo to return in order to finish the painting commissioned of him. Charles d’Amboise, the deputy of Louis XII of France, replied to the Florentine authorities on various occasions, defending the artist and obtaining two postponements of his return to Florence. In January 1507, on two different occasions, the King of France explicitly stated his intention of keeping Leonardo beside him, and commissioning him to paint a number of works. When, in a letter dated July 26, Louis XII referred to Leonardo as «notre paintre et ingenieur ordinaire», it was clear that the Battle of Anghiari would never be finished.

In Milan, Leonardo dedicated himself to anatomical studies, while painting several works during this same period.

They were tumultuous years, in which the artist was embroiled in a lawsuit against his half-brothers for the heredity left him by his uncle Francesco. Meanwhile, the lawsuit with the Confraternity of the Immaculate Conception, over the Virgin of the Rocks finally reached a conclusion.

It was only with the return of the Sforza dukes to Milan, in 1513, that Leonardo abandoned Lombardy, moving to Rome at the service of Giuliano de’ Medici, son of Lorenzo the Magnificent and brother of the newly elected Pope Leo X.