Patrick and the CBI team investigate the murder of a tutor, and find a mysterious little red box near the body, starting a chain of events that turns the murder into the search for a priceless ring stolen from the British Museum. Meanwhile, Lisbon is worried when a new boss, Madeleine Hightower, takes command of the CBI, as well as mysteriously learning about Rigsby and Van Pelt's relationship.
Cristina won't let herself get excited when she is nominated for a Harper Avery award; Alex thinks about making a change; Callie and Derek work with a machine that recognizes emotions.
The doctors are exposed to flu-infected patients; Derek prepares to give a speech; a new doctor gives Alex a glimpse into an alternative medical practice.
Cristina enlists Meredith to help her prepare an acceptance speech for her possible Harper Avery win and while Owen offers to attend the ceremony with her, she insists on going alone. Meanwhile, Derek feels overwhelmed between his responsibilities at home and at the hospital. April and Jackson come to a disagreement on children and religion, and Callie and Arizona try to reconnect in their marriage.
Jackson is given the daunting task of delivering disappointing news to the doctors. Meanwhile, Derek's sister Amelia drops by for a surprise visit, Richard surprises Catherine in Boston and when Bailey gets frustrated by the slow pace of her research, she makes a risky decision.