A quadriplegic ex-forensics expert, Lincoln Rhyme (Denzel Washington) and a rookie patrol cop, Amelia Donaghy (Angelina Jolie), team up to solve a string of murders all connected to one killer by his signature: a single shard of bone is removed from each of the victims. Rhyme is bed-ridden, but communicates with Amelia via phone as she examines the various crime scenes and collects evidence and reports back to him.The killer poses as a New York taxi driver, and abducts and kills those who get in his taxi. The first two victims are a married couple named Alan and Lindsay Rubin, who get a taxi home but then find themselves kidnapped by the killer. Amelia finds Alan's body buried in a Civil War-era railroad bed. She also finds a piece of shellfish, which eventually leads Amelia - working with Rhyme - to Alan's wife, and a scrap of paper. The detectives find Mrs Rubin, too late, at a steam junction in a below ground services area of a building in the financial district, secured at the mouth of a pipe which emits steam using old handcuffs or shackles. She has been scalded to death from the steam. The killer has also removed a bit of flesh and bone from her arm. Amelia finds another scrap of paper at the scene.The killer then abducts an NYU student. He is taken to a derelict slaughterhouse where he is tied to a pole and gutted with a knife, and left for rats to feed on. Amelia and Rhyme, using the clue left by the killer at the scene of Lindsay Rubin's death (rat hairs embedded in a bone from a cow's body), find the victim, but again too late to save him. Again, the killer has removed a piece of the victim's bone. Amelia is able to collect the evidence, including another scrap of paper. The pressure of the tense investigation and bureacratic challenges to both Amelia's and Rhyme's involvement with the case are having serious impacts on Rhyme's health and stability.After piecing together the message the killer was sending using the scraps of paper, Amelia and Rhyme are led to an old book of short stories, which in turn leads them to the killer's next victims, a grandfather and granddaughter tied to a pier as the tide rises. The girl is rescued, but her grandfather dies. At the scene, Amelia finds another bone, an old police badge, and an old subway map. These clues, and an earlier clue left by the killer at the scene of Mrs Rubin's death (asbestos) lead Amelia to an abandoned subway station, in which Amelia sees some numbers which have been tampered with to spell out Rhyme's police badge number. Amelia then figures out that the bone collector is after Rhyme.The bone collector arrives at Rhyme's house, and after killing Rhyme's nurse Thelma and Captain Cheney (Michael Rooker) it is revealed that he is the medical technician who cares for Rhyme's medical equipment. The technician, Richard, is an ex-forensic cop who wants revenge because in the past, Rhyme's testimony helped convict the killer of planting false evidence at crime scenes. The result is that the killer was brutalized in prison and his life ruined. Despite the helpless state he is in, Rhyme manages to jam the killers hand by flapping his bed horizontal, and in struggle to free himself, the killer pulls Rhyme with him and they both collapse to the floor. Rhyme then manages to bite the killer in the neck, causing massive bleeding (in fact, in the novel, Rhyme kills him by severing off his spinal cord). Richard once again manages to free himself, grabbing a large knife and about to end Rhyme's life, Amelia suddently arrives at the apartment with a gun, killing him before he has a chance to deliver the fatal stab. The film ends at a Christmas celebration at Rhyme's apartment. Rhyme, having given up his plans to end his life by suicide, faces his sister and niece coming to visit him along with Amelia, Paulie and his family, Eddie and his mother, and Lincoln's new nurse.