- Quentin "Q" Jacobsen: The protagonist and narrator of the story. He has had a crush on his neighbor, Margo, since they were kids. Throughout their childhood and adolescent years, his crush on Margo develops. In the book, Quentin realizes his love for Margo, particularly after her disappearance. He tracks clues that he thinks Margo has left behind for him to help him find her. Quentin soon becomes obsessed with finding these clues and recruits his friends to help him find Margo. His desire to find Margo results in him neglecting school and his friends, which Radar rebukes him for. His obsession, in turn, causes him to possess this fantastical and essentially perfect image of Margo. Towards the end of the novel, he discovers that his image and expectations of her were unreal.
- Margo Roth Spiegelman: A self-described "paper girl" who runs away from home only to be pursued by her childhood friend, Quentin. Margo is one of the most popular girls at her local high school. Due to her unhappiness with the "falsity" of her setting, she decides to leave town. However, before she leaves town, she enlists Quentin to help her fulfill a revenge plan on everyone that has mistreated her. In the beginning of the novel, she discovers that her boyfriend, Jase, is cheating on her with her best friend, Becca. In the past, Margo has run away from home four times. She has a love for American literature, music, and travel. Her pet dog, Myrna Mountweazel, is a reference to Lillian Virginia Mountweazel, a woman who never existed, but was listed in the 1975 edition of the New Columbia Encyclopedia.
- Ben Starling: He is one of Quentin's best friends. He is in the school band and also helps Quentin find Margo. In the process, he becomes Lacey's boyfriend. In the beginning of the novel, Ben has an obsession with prom and refers to girls as "honeybunnies". During prom weekend, Ben becomes the individual with the longest keg stand in Winter Park history by sixty three seconds. He drunkenly makes a deal with Quentin and Radar to wear nothing underneath their graduation robes. Throughout the novel, Ben strives for conformity. Like Radar, Ben also criticizes Quentin for his Margo obsession.
- Marcus "Radar" Lincoln: He is one of Quentin's best friends. In the novel, he is constantly editing pages on a website called Omnictionary, which is ultimately a parody of Wikipedia. He was nicknamed by Quentin and Ben after the character from M*A*S*H. To his embarrassment, his parents own the world's largest collection of black Santas. He is in the school band. Like Ben, Radar assists Quentin in finding Margo. He is dating a girl named Angela. Throughout the novel, Radar often possesses the most insight about Quentin. He even criticizes Quentin for his Margo obsession and selfishness.
- Lacey Pemberton: She has been one of Margo's closest friends since kindergarten. However, Margo and Lacey have a strange friendship. Margo feels that Lacey has always been judgmental of her throughout the course of their relationship. In the beginning of the novel, Margo vandalizes Lacey's car out of anger at the fact that Lacey did not tell her about Jase and Becca. However, Lacey was unaware of their relationship. When Margo disappears, Lacey becomes concerned and involved in the search. She befriends Quentin, Ben, and Radar to help look for Margo. Lacey even has her cousin place flyers all over New York City, a place where Margo supposedly told her ex-boyfriend that she wanted to go, in search of her. In the novel, Lacey becomes Ben's girlfriend and prom date. Her character develops more towards the second half of the text, as she becomes more involved in the search for Margo. She even skips graduation to go with Quentin, Ben, and Radar to find Margo.
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