A Study in Charlotte is Brittany Cavallaro’s first novel in a series featuring Charlotte Holmes and Jamie Watson, the descendants of Sherlock Holmes and John Watson. Through some machinations of Jamie’s estranged father, the pair end up attending the same boarding school in rural Connecticut. Both teens struggle with isolation and loneliness. Though their friendship has a rocky beginning, they find common ground in their distaste for sophomore bully Lee Dobson. Ironically, Jamie ends up in a fistfight after the rugby player says ugly things about Charlotte.

When Lee turns up dead a few days later, Jamie and Charlotte are the chief subjects, particularly because the murderer staged the killing to resemble a classic Sherlock Holmes story. Their friendship grows over their combined efforts to clear their name. For a while they are working against a local policeman, Detective Shepard. One night, after a late night run to a local diner, the teens emerge from the building to find that they were being tailed by a man that resembled the local drug dealer. A car chase ensues through the country roads, and eventually his car flips. At that point, the man takes off running into the woods. They lose him, but not before Charlotte notes that the man is not local; he is too well trained and well-dressed to be anyone but an employee of a powerful European family.

Eventually, another student is attacked during the homecoming dance. The second victim’s attack is likewise made to look like a Sherlock Holmes story, and the detective is almost ready to arrest the pair. In the crowd that gathers around the victim, Jamie and Charlotte see the mysterious figure again. With the local police at their heels, they chase him to a room underground where someone has assembled information on the victims. Indeed, it looks precisely like a killer’s lair, complete with notes written in Charlotte’s handwriting.

It would be convincing, if Charlotte Holmes were not too intelligent to have such an obvious room. The teens are arrested anyway. After Charlotte confesses to her intermittent drug use, the police are forced to let the teens go home with Jamie’s father. The next day, the detective comes over to arrest them again, but they are saved by a report that Charlotte’s roommate is attacked. The attack is again similar to a Sherlock Holmes story. However, it is familiar enough that once the detective leaves, Jamie is certain that Charlotte staged the attack to prove to the police that they are innocent.

Detective Shepard gives the pair a month to come up with evidence of their own. For several weeks Jamie and Charlotte investigate. Jamie is certain they should be paying attention to the Moriarty family—a family with a longstanding feud against the Holmeses. Moreover, there is a hint of a scandal involving Charlotte and the youngest Moriarty, a brilliant maths student named August. However, Charlotte refuses to speak about it, and Jamie promises not to pry. Their digging takes them in the way of an over-curious English teacher and a too-friendly nurse.

The climax arrives when Charlotte and Jamie get into a terrible fight. When Jamie returns to his dorm, he finds that his room has been bugged. Driven by rage, he nearly destroys his room in the search for the camera and recording device. By the time he is successful, he hears a commotion outside. A bomb has erupted in the science building, exactly where Charlotte’s lab is located. Jamie runs across campus to try to find her safe; eventually, he does find her alive, and his father takes them back to his house.

By now, the students know their lives are in danger. The school decides to close for the remainder of the semester, promising to briefly open the next day so that students can claim their belongings from their dorms.

In the interim, Jamie feels forced by Charlotte’s reticence to use his father’s store of information; he learns about the scandal involving August. August, who was hired by the Holmes family to tutor Charlotte in math, eventually became close enough to Charlotte that she developed a crush on him. When he rejects her—he is quite older and has a fiancée—she arranges for him to get caught buying her drugs. As a result, he is expelled from school and forced to work a shadowy job in Europe. Jamie is more convinced than ever that they should be looking at him.

When Charlotte realizes that Jamie snooped, she runs off and takes oxycodone. Jamie finds her high and bitter and fearful about their friendship. She talks about August, and Jamie listens patiently until he makes the connection between August’s fiancée and their school nurse.

Charlotte’s brother Milo, a powerful and wealthy government agent, is on his way to them. He confirms that August’s fiancée was named Bryony—the same name as the nurse. They make plans to inspect her apartment the next morning.

When they arrive, they are met by Charlotte’s brother Milo. Jamie goes back to his room to get his things and falls prey to a trap the nurse set: a spring-loaded dart that is infected with a deadly virus. She gives Charlotte and Milo twenty-four hours to give her immunity and a suitcase of cash, in exchange for the antidote.

Jamie falls very ill. When it appears he will die, Charlotte kisses him and promises to try to love him. Bryony comes over the next morning, and Charlotte and Milo expose her employer—August’s brother Lucien—and find where Bryony has hidden the antidote. Jamie is saved. The teens make plans to stay together.