The film opens during Spring Break on the Upper East Side. White Mike, once a wealthy, carefree teenager, now struggles to scrape out a living as a pot dealer, dealing to his former classmates. His mother died from breast cancer a year prior to the events of the film, her treatment having completely consumed his family's wealth, and left a deep emotional trauma on Mike. Mike's good friend, Molly Norton, a sweet girl from the poorer side of town, doesn't know he is a drug dealer. Mike's supplier, Lionel, also deals the addictive drug cocktail "Twelve" to Mike's cousin, Charlie. Charlie attempts to mug Lionel one night, as he is unable to pay for the drug. Lionel turns the gun on Charlie, shooting him at point blank range, before finding and executing Nana, an innocent observer, returning home after a basketball game at the Harlem Recreation Center. Mike and Charlie's good friend, Hunter, another resident of the wealthy Upper East Side, set on attending Harvard, who had played basketball with—-and got in a fight with—-Nana earlier that evening, is taken into custody for the murders. He visits Harlem regularly because he detests the high society of his classmates.
Several of the other young residents of the wealthy Manhattan scene are introduced at a party as customers of White Mike, including male model Tobias and several others, all of whom know the attractive and popular Sara Ludlow. The party is held at the home of Yvette Vasquez and Chris Kenton, a hopeless nerd, but the host of the party, which he threw in order to boost his popularity. At the party, Sara's friend Jessica Brayson tries Twelve for the first time, leading to an addiction over the course of the film. During the party, Chris's older brother, Claude, a sociopath and weapon collector, returns home after breaking out of rehab, much to the dismay of their mother. She realizes he is there while Chris is videoconferencing with her, and threatens to call the police. Chris tries to mediate and asks her to talk with Claude. She says she will speak to him but disconnects—with a swallow of pills—when Chris leaves the room. Sara's birthday is coming up just before the end of spring break, and she easily manipulates Chris into throwing a huge birthday bash for her, hinting that she will compensate him with sex—something she has no intention of doing. She and her friends Shelly and Gabby spend the next few days inviting everyone they know in order to make Sara's birthday "famous."
Meanwhile, Jessica has run out of money as well as Twelve, but asks Lionel (her Twelve dealer, whom Mike had introduced her to) to stop by Sara's party, anyways, so she can buy more Twelve. Tobias accidentally meets Molly during a drug deal with Mike, and invites her to Sara's party. Mike sees him from across the street and phones him to pick up the weed he had wanted. With Tobias gone, Mike meets with Molly, where she tells him about the male model who she allowed to flatter her and who also invited her to a party tonight. They relax over hot chocolate until she suggests visiting him at his job that evening; Mike closes up and dashes off after only a few minutes of talk. Molly is disappointed and decides to go to the party Tobias invited her to.
As the party begins, Claude locks himself in his room, practicing with his weapons, as the noise grows louder downstairs. Tobias disappears into one bedroom with a girl. Lionel arrives, but is infuriated that Jessica does not have the money she promised. Since she has no money, she first offers him a blowjob, to which he responds that it must be "one expensive blowjob." Tearfully, she offers to have sex with him, revealing furthermore that she is a virgin. Lionel agrees and they head inside. Tobias heads back into a bedroom with a different girl. Mike's father calls him to deliver the news that Charlie is dead, his body finally having been identified. Mike tries to call Molly, who doesn't answer her phone. He goes to the party to locate her, but is stopped by several drunk party-goers. He accidentally enters the wrong room, only to find Jessica and Lionel having sex.
Lionel, startled, pulls out a gun, which Mike recognizes as Charlie's. As he begins to accuse Lionel of the murder, Lionel shoots him, causing Claude to pull out his weapons and begin shooting up the party. Tobias is shot in the eye and Lionel is shot and killed, along with Sara and Timmy. Timmy was with Mark Rothko as they frequently tried to buy pot from White Mike. Teenagers rush out of the party, but many others are shot and killed. Claude calls out for Chris, who is hiding in the kitchen, when he hears police sirens. Claude hears them too and runs outside to die in a suicide by cop fashion. As she lays dying, Sara's last thought is how this will now make her famous.
As Mike wakes up in the hospital, Molly reprimands him, having finally found out about his drug-dealing livelihood and the power he holds over the people he deals to. He wants to call her when he is sent home, but she says not to; not until he is done with this life. As the film closes, Mike visits Nana's mother, and together they connect over their shared grief—Mike, finally coming to terms with the loss of his mother, and Nana's mother, coping with the loss of her son.
Twelve premiered at the 2010 Sundance Film Festival.
The film opened on August 6, 2010, and earned a domestic total of $183,920 in a release of a mere two weeks. The film grossed $2,299,357 in foreign territories, adding up to $2,483,277. Based on an estimated $5 million budget, the film is a box office bomb.
The film received largely negative reviews, currently holding a 3% rating on review aggregator website Rotten Tomatoes, based on 30 reviews. On Metacritic, the film has a 22/100 rating based on 13 critics, indicating "generally unfavorable reviews".
The film has been referred to as "the worst movie in the history of Sundance". In his review in New York Times, Stephen Holden writes:
The DVD was released on December 28, 2010; the only special features include previews for Mirrors 2, Predators, Vampires Suck, The A-Team, and Wall Street: Money Never Sleeps.