Laura Morelli's novel The Night Portrait centers around Leonardo da Vinci's famous painting Portrait of a Lady with an Ermine, the “night portrait” of the title. Four characters interact with this painting throughout the novel: the portrait's subject Cecilia Gallerani and Leonardo da Vinci himself (both in 1492) and Edith Becker and Dominic Bonelli (during World War II). For these characters, the portrait symbolizes the darkness of their lives.

For Cecilia, the painting is a night portrait, for it records a time in her life when she is a mistress to the Duke of Milan. She is only sixteen years old, but she is caught up in forces well beyond her control. Cecilia's dowry is gone, so she has little hope of marrying (even though she wants to be the Duke's wife). She must, therefore, fight her way through palace intrigues and struggle against those who would like to see her cast out.

Leonardo da Vinci experiences his own struggles as he tries to make his mark on the world. He must remain in the Duke's favor if he is to receive patronage to fund his projects, so he paints Cecilia's portrait.

Edith Becker is an art conservator who mistakenly turns this priceless portrait over to a Nazi and then struggles to fix her error and retrieve the painting at great risk to her own life. The portrait thus symbolizes the “night” of her mistake and her dangerous quest.

Dominic Bonelli is a US soldier and one of the Monument Men who works to restore pieces of art to their rightful owners. He helps Edith track down the portrait, but as an artist, he is disgusted and discouraged by the scenes of war and corruption he has been experiencing for so long. Therefore, the portrait symbolizes his own dark night as well.