"Painting Mona Lisa" offers an explanation behind the mysteries surrounding da Vinci's famous portrait – why did Leonardo keep the "Mona Lisa" with him until his death? It is April 26, 1478. Lorenzo De Medici, the head of the powerful Florentine Medici family is attacked. He survives, but his younger brother, Giuliano, dies beneath multiple dagger blows. Ten years later, a young Lisa Gherardini listens to her mother retell the story of Giuliano's death, sharing her mother's passion for the arts, and even attending some of the Medici gatherings. But, her father – a follower of the fanatical Dominican monk Fra Girolamo Savonarola – scorns the wicked paganism of the Medicis. Lisa becomes the lover of Lorenzo's son, Giuliano the younger, just as the French king arrives to banish the Medicis from Florence, beginning the reign of the fire-and-brimstone preacher. As they flee, she is forced to marry Francesco, a pious but cruel man. Florence's citizens rise up and hang Savonarola. But even after the friar's execution, the Medici remain banned. Leonardo da Vinci is commissioned to paint Lisa's portrait. Having tasted Borgia politics, Leonardo is now acting as the Medici family's agent in Florence. He aims to discover the leaders of the Savonarola underground – working to reinstate their strict theocracy, but also intends to find the man involved in the 1478 murder of Giuliano de Medici the elder. Confessing his love for Lorenzo's brother to Lisa, he tells her that she has reignited the flame in his heart, for his lover's murderer was her the man she though was her father, not one of the conspirators, but a furious husband seeking revenge on his wife's lover. Lisa he helps Leonardo report her father's and husband's to the authorities and together they flee Francesco's revenge and travel to Rome and her half-brothers. Along the way, Lisa and Leonardo make love! Lisa yearns for another child, and Leonardo desperately longs to have his dead lover's child.