Portrait of an Unknown Woman opens early in 1527 with the arrival of painter Hans Holbein at the home of the More family. Sir Thomas More has recently been named Lord Chancellor by King Henry VIII, and things are looking up for his family. To celebrate, he has commissioned Holbein to paint a family portrait.

Holbein's arrival coincides with a visit from the family's former tutor John Clement. Meg Giggs, More's adopted daughter, has been in love with Clement since her teen years, when they bonded over trips to the herb sellers, for Clement is a physician and Meg is fascinated by herbal cures.

Thomas More has planned carefully for his children's futures. He already knows who is going to marry whom, and that plan includes Meg and John Clement. He knows that they are in love with one another and that is also part of the plan. But John has a secret, and More refuses to allow them to marry until the secret has been passed to Meg.

Meanwhile, Holbein, whose painterly eye sees truth, has himself fallen in love with Meg, despite the wife and children left behind in his native land.

The novel is set against the turbulent backdrop of the Protestant Reformation and framed by Holbein's two very different portraits of the More family, done five years apart. More, as Henry VIII's chancellor, uses his power to stamp out Bible-men (those who believe in translating the Bible from Latin into English so the common people can understand Scripture). Meg becomes alarmed when her father becomes increasingly cruel -- though never with his family -- especially when he orders the burning of a family friend for heresy. But when More falls out of favor with Henry, what will happen to his family?

The story intertwines Meg and John's romance and marriage with Holbein's growing realization that he is hopelessly in love with Meg. Even after the portrait is finished, with commissions from important people at court, he has trouble concentrating on anything but her. When secrets from John's past and Meg's increasing involvement with the Bible-men threaten to tear them apart, it seems as though Holbein just might get his chance.

Despite the violence of the age, and Meg's growing inner turmoil, the novel is a gentle one. More does his best to shield his family from the political situation and always appear to them as the same good-humored, intelligent man they have always known. And though Meg knows better, she tries not to let the knowledge taint her relationship with her father.

Portrait of an Unknown Woman is not a sweeping historical epic, but the story of how politics, religion and secrets influence one family's lives. The book includes a bibliography, a section titled "The History Behind the Story," which discusses the period's religion and medical knowledge, and a list of museums where Holbein paintings can be found.