Three police officers, Detectives Poley (William Fichtner), Frizer (Thomas Kretschmann), and Skeres (Delroy Lindo) are interrogating Ned Cruz (Antonio Banderas), a Los Angeles private investigator, who tells them that five years earlier (featured in a series of flashbacks), Russian mobster Skinny Faddeev gave $30 million in blood diamonds as an advance to Anton (Robert Maillet), a boxer, to intentionally lose a fight against his nephew. However, during the fight, Anton unintentionally killed the nephew. When Skinny was found dead, Anton was sentenced to life in prison. While Anton was in prison, he received over 200 letters from a woman named Lexie Persimmon. Anton escaped from prison five years later and is determined to find Lexie.In the present day (in another series of contemporary flashbacks) Anton approaches and gives Ned the job of finding Lexie. Ned is skeptical about his job, since he doesn't have a photo of Lexie. As he starts investigating the various clues, people start dying mysteriously.Ned first interviews actor Adam Nova (James Van Der Beek) whom he had worked for in the past about trying to keep secret Nova's sex life. Nova dies when his house explodes.Next, Ned interviews a certain Zooey Wigner (Rebecca Mader) at a local hospital who is being treated for drug withdrawal about Lexie and who used to work at the strip club where Lexie supposedly worked. Zooey is found dead the next day in her apartment having been drowned in her bathtub.Ned talks with a porn producer/director named Puss (Snoop Dog) about the women that work for him and about the woman Lexie. Puss is found the next day dead from a broken back.Ned also notices that a black Lincoln is following him, which he assumes is the Russian Mafia. He finds a clue from a discarded letter that Anton had given him that leads him to believe that Lexie might be in San Celeritas, New Mexico.In New Mexico, Ned meets a tattooed waitress named Fay Neman (Autumn Reeser)--a particle physics buff--who helps him. Fay seduces Ned in his motel room for some "organic" function experiment.Ned also meets Simon (Sam Elliott), his wife Julie (Sienna Guillory), and Niels Geck (Jimmi Simpson), a physicist who is conducting an experiment for Simon. Simon is interested only in finding the "God particle" and feels indifferent when Julie tries to warm up to Ned. Ned suspects that Julie might really be Lexie and decides to tell her what is happening.Meanwhile, Anton tracks down Ned to Simon's bungalow. Ned confronts Julie with his suspicions about Lexie's true identity, but Julie has no idea what he is talking about. Ned and Julie hear gunshots, causing Ned to suspect that Anton is at the house.Realizing that he and Anton have both mistaken Julie for Lexie, Ned tries to save her. When the duo head toward the basement, Ned is astonished to find Niels dressed like a woman, and in a blonde wig. A box containing cosmetics has the phrase "Lex Parsimoniae"--a Latin phrase meaning "When all things are equal, the simplest solution is the best"--printed on it. Ned realizes that Niels had written the letters to Anton, who becomes angered when Niels tries to convince Anton to accept him. In a shootout, Ned is injured and passes out.The story cuts back to the present day, where it is revealed that Niels and Anton killed each other while the detectives, who had followed Ned to Simon's house, held Ned and Julie hostage. Julie is kept bound and gagged with duct tape. Ned accuses the trio of following him and killing the people he met, also stating that Skinny was killed for diamonds, which his killer never recovered. Ned proves that Frizer alone killed all the people who could have known about the diamonds. Frizer admits his crimes, for which the other detectives scold him. Ned looks at a glass tank containing a gecko and realizes something; he tells the villains that he knows where Niels stored the diamonds.The detectives take Ned and Julie to the spot where he had confronted Julie after she had shown him a hidden shoe-box. While Julie and Ned are in the car, Skeres and Frizer go to get the shoe-box. Meanwhile, Poley spots Julie and Ned signaling each other. He attacks them, but they overpower him and manage to drive the car towards Skeres and Frizer. Skeres and Frizer are disappointed when they discover the diamonds are not in the box. When they see the car coming towards them, they realize what is happening and start shooting. Ned shoots them both dead. Meanwhile, the physicist Simon's experiment destroys his lab and creates a giant crevasse. Ned and Julie speed away in the car, and they later pick up Fay, who happens to be their co-accomplice.