The credits appear over newspaper articles and photos detailing the successful career of forensic expert Lincoln Rhyme (Denzel Washington). One story details Rhyme's involvement in convicting a cop.
Rhyme is investigating a transit cop's death in a sewer tunnel when a falling concrete beam crushed him. He wakes up in a hospital bed, a quadriplegic. A man and his wife (Gary Swanson and Olivia Birkelund) are at the curb at the airport early in the morning, looking for the person they expect to pick them up. When their ride doesn't show, they take a taxi. The cab driver kidnaps them to a desolate part of town, but before we learn more Rhyme wakes up in his apartment which is fully equipped to manage his medical care. Rhyme's medical tech Richard Thompson (Leland Orser) tells him his heart monitor is faulty.
Dr. Barry Lehman (John Benjamin Hickey) arrives to talk about Rhyme's request for assisted suicide. He agrees to help Rhyme the next weekend. His nurse, Thelma (Queen Latifah), listens and watches.
Amelia Donaghy (Angelina Jolie) is brooding by the window of her apartment. She's a patrol cop and her boyfriend (Bobby Cannavale) pressures her to make a commitment to their relationship, but she refuses. On the street, she responds to a radio call and finds the man from the cab buried in the rocks, with only his hand showing. One of his fingers is missing. On the nearby railroad tracks she sees a pile of sand, a note, and a bolt. She stops an oncoming train and ask Chris (Christian Veliz), the boy who reported the dead man, to buy her a disposable camera. She photographs everything including a footprint nearby.
A masked man is dragging the woman from the cab through underground tunnels. She is handcuffed and gagged. He attaches the handcuffs to chain around a pipe and leaves her.
Captain Howard Cheney (Michael Rooker) arrives at the crime scene and meets Detective Solomon (Mike McGlone), then is directed to Donaghy. She gives the evidence she collected and the camera to Detective Paulie Sellitto (Ed O'Neill). Cheney dresses her down for stopping the train.
Rhyme is visited by Sellitto and Solomon, who describe the crime scene to him. The victim's name is Alan Rubin, a wealthy NY builder worth several million dollars. His wife's wedding band was forced onto one of his fingers, stripped of flesh. Rhyme believes it's a kidnapping and a ransom demand will be forthcoming. Rhyme has a seizure and passes out.
When he wakes up, he looks at the evidence and crime scene photos left behind by Sellitto on a large monitor. The note is a torn page from a book. The page number is 119. There's a newspaper clipping from 1913 with 4PM circled.
Donaghy is receiving an introduction to the youth services division that she has just transferred into. Rhyme has her pulled out of the training session and, when she arrives, he praises her excellent forensic work and photography. She says she read his book in the academy. He believes the book page number and time refers to the current day's date, three hours from now. Rhyme thinks the man's death scene is staged and that it indicates the woman will be killed at 4:00. He asks Donaghy to help on the case. She refuses, but her boss overrides her. The cops set up workstations and desks around Rhyme's spacious apartment.
In the tunnels, a masked man shaves a wooden stick and looks at a pocket watch. The kidnapped woman, Lindsay Rubin, her mouth covered in duct tape and her wrists handcuffed to the pipe, watches.
The investigators learn that the bullet taken from Alan Rubin was from an old Webley pistol. The bolt has three initial "NSG" embossed on it, and it's not steel, but iron, meaning it too is very old. They also look into the asbestos found at the crime scene. Rhyme tells Donaghy to identify all locations where asbestos is currently being remediated in Manhattan.
Crime technician Eddie Ortiz (Luis Guzman) arrives and sets up a portable forensics lab. Eddie finds a scrap of very old paper on the bolt. The sand appears to be ground up oyster shells. Rhyme remembers a police case from 1913 where a body was found in crushed oyster shells in downtown Manhattan, near the Woolworth building.
Rhyme asks Donaghy to investigate the area, encouraging her to trust her instincts. As they drive there, Sellitto tells Donaghy about Rhyme's superior expertise in forensics, his interest on collecting eclectic stuff, and examining it. She asks about his family, and Sellitto says he has cut off contact with his only sister.
Underground, the masked man loosens another bolt from a steam pipe. He rotates a very large pipe around so the opening faces Lindsay Rubin. Eddie tells Rhyme that the iron bolt was primarily used for assembling steam pipes. . Rhyme tells Sellitto that there is a steam junction in downtown Manhattan where steam is released from the pipes everyday at 4:00 pm. Rhyme tells Amelia to put on a radio headset and prepare to enter the steam tunnels to work the crime scene if Lindsay Rubin can't be rescued. Donaghy enters the sewer tunnels. The Department of Steam is unable to turn the apparently frozen valve. Donaghy can hear Lindsay Rubin, but a new wall of construction blocks cuts off access. The steam pipe workers break the steam valve and learn it has been tampered with. Lindsay Rubin is burned to death.
An Emergency Services team blows an opening in the concrete block wall. Donaghy enters and describes the scene in detail to Rhyme over the radio. Donaghy is terribly upset when she sees Lindsay's burned corpse. She finds a piece of wood, hair clippings, and a bloody bone shard. Under Rhyme's direction, she tells Rhyme that Lindsay was bound with old-fashioned shackles, with a chain around her waist, and a rope around her feet. Lindsay has a surgical-style wound on her forearm. Rhyme wants her to saw off the hands to preserve the cuffs. Donaghy tries but then refuses and goes home. Rhyme researches Donaghy's background and learns that her father, a cop, committed suicide, and that Donaghy found the body. Det. Solomon goes to Donaghy's apartment, but when she doesn't answer the door, he tries her window. Donaghy arms herself and nearly shoots Solomon. He tells her that Rhyme believes the evidence she collected indicates there's another victim in play, and that Rhyme needs her help.
Outside a nightclub, a student (Danial Brochu) gets into a cab and disappears. A witness reports that she saw the cab driver hit the student before driving away. The taxi driver takes the bound and gagged student to an abandoned building. The masked man ties the student to a post at floor level and cuts him repeatedly.
Rhyme's team discovers the bone fragment is from bovine, from a cow, and discover more old newspaper embedded in it. The hair is from a rat, shaved. Donaghy suggests that the perp might be a cop. Rhyme tells the team to look for the location of old stockyards and slaughterhouses.
Rhyme sends a team to one of the old slaughterhouses, decommissioned in 1898. Donaghy goes in first and finds the dead student. He has been eaten by rats attracted to the numerous bleeding incisions. Donaghy describes the scene to Rhyme, while the team outside tries to delay the NYC ESU unit, led by an official in contact with Cheney, from contaminating the area. The student is missing a chunk of flesh from his leg. Donaghy finds a matchbox and a piece of old paper. Cheney removes Rhyme from the case, but Rhyme tells Ortiz to continue his research.
Captain Cheney's team finds a finger print and match it to a taxi driver with a criminal record. They raid his repair shop only to find him dead under a vehicle and missing a finger. Cheney demands Donaghy turn over the evidence she collected, but she demands a chain of evidence receipt, which Cheney refuses to provide.
Donaghy takes the evidence to Rhyme. Ortiz produces records of old unsolved homicides that include evidence of missing flesh. Each homicide also had a message buried in the evidence, but no one noticed. Rhyme has another seizure and passes out. Thelma tells Donaghy about Rhyme's request for assisted suicide, and while Donaghy waits for Rhyme to wake up, she looks at his badge, awards and photos. Cheney tries to see Rhyme, but Thelma refuses to allow him to enter, and Cheney vows to come back with a warrant.
A grandfather and his granddaughter get into a taxi at the airport. A taxi inspector stops the taxi and questions the taxi driver about why his flag is down. The driver kills him and speeds away. The little girl screams.
Sellitto calls Rhyme to report the taxi incident, while Rhyme examines the paper clippings, uncovering a logo from an old book publisher. Amelia goes to a bookstore and finds a book called, The Bone Collector, which contains stories describing the murders already committed. One of the final chapters illustrates a man and girl hanging from a rope over water. Rhyme thinks the odd smell from the paper is diesel, and he remembers an old diesel refueling station on Staten Island. Amelia searches for and finds them tied to a pier, drowning under the rising tide. Rescue crews are unable to resuscitate the grandfather, but the little girl survives.
Donaghy looks for clues and finds a map, a bone, and a piece of metal that looks like a cop's badge. The map shows an old subway map, and Rhyme thinks the killer is at the southernmost station. Cheney arrives and Amelia sneaks off to the station described by Rhyme. There are footprints in the abandoned station, and she finds a train numbered 78499. She tries to remember the number, and realizes it's the same as Rhyme's police badge number that she saw earlier at his apartment.
A man knocks at Rhyme's apartment door and when Thelma opens the door, he stabs and kills her. Someone enters the apartment and washes their hands. Richard Thompson, the medical technician who has been maintaining Rhyme's medical equipment, appears. He says Thelma is in the hall, but when the phone rings, he yanks the phone line and disconnects the power to Rhyme's monitor. Thompson reminds Rhyme of a forensics cop in Syracuse, New York, named Marcus Andrews who was suspected of doctoring evidence to obtain false murder convictions. Rhyme's expert testimony put him in jail for six years. Thompson / Andrews tells Rhymes that as a cop he was brutalized every day while in prison. When Thompson / Marcus tries to lower the bed, Rhyme uses his mouth control to suddenly lower the bed and trap Thompson / Marcus' hand. Thompson / Marcus pulls his hand out, but his fingers are mangled. He pulls Rhyme off the bed and as he prepares to stab him, Rhyme bites him in the neck. Thompson / Marcus retrieves a carving knife, and as Thompson / Marcus prepares to stab Rhyme, Donaghy appears and shoots Thompson.
Sometime later, Rhyme is using a motorized wheelchair and living with Donaghy. It's Christmas, and all his friends show up, including his estranged family and niece.