In Milan, in 1506, Leonardo da Vinci is arrested on charges of having poisoned Caterina da Cremona. After declaring his innocence to Stefano Giraldi, an official of the Podestà, Leonardo recalls his days as an apprentice in the workshop of Andrea del Verrocchio, where he first met the model Caterina.

Leonardo moves to Milan, determined to obtain the patronage of the Regent Duke Ludovico Sforza. When reality proves to be less attractive than expected and Leonardo is asked to devote himself to a great theatrical performance instead of a painting, it is a new encounter that helps him to free his imagination, allowing him to see in the theatrical production a great opportunity.

Following the death of Ludovico's wife, Leonardo is assigned a new commission but struggles to deal with his inner turmoil; after taking on board some wise words from Fr. Luca Pacioli, Leonardo seeks assistance.

Having found Caterina, Leonardo continues his work, but is frustrated by the growing success of a younger artist, Michelangelo Buonarroti. Putting his feelings aside, Leonardo allows himself to be persuaded to accept a new commission.