The fourth installment in the Alex Cross series finds Cross, a homicide detective and psychologist in Washington, D.C., caught between two deadly adversaries: a resurfaced killer from his past and a mysterious murderer terrorizing Europe.
Gary Soneji, a kidnapper and murderer whom Cross previously captured, is free and has returned to Washington with plans to kill Cross and his family. In a prologue, Soneji breaks into the cellar of the Cross home on Fifth Street, handling the family's belongings in the dark and fueling his hatred. Meanwhile, in London, a killer known as Mr. Smith performs a live autopsy on a chief inspector. Smith, so named by the Boston press, has murdered over a dozen people across America and Europe, and police speculate that no human could commit such acts.
Cross, narrating in first person, finds himself drawn to Christine Johnson, the principal of the Sojourner Truth School where his children, Damon and Jannie, attend. Christine's husband, George, died the previous winter, and Cross is emerging from years of grief over the death of his own wife, Maria. That morning, Soneji drives to Union Station, sets up a Browning automatic rifle with an electronic timing device on a balcony, and opens fire on commuters.
Cross receives a taunting phone call from Soneji and races to the station with his longtime partner, Detective John Sampson. They find the rigged rifle firing in programmed volleys, but Soneji has already escaped aboard the Metroliner in disguise.
That evening, Cross and Christine have their first dinner date. The evening is effortless, but Christine abruptly says she cannot date Cross; her husband's violent death has left her unable to risk closeness with someone in dangerous police work.
Soneji travels to Wilmington, Delaware, and murders his estranged wife, Missy. Cross and Sampson later find Missy's severed head affixed to the family's decapitated dog. They discover Soneji's daughter, Roni, alive but bound in a cellar closet, echoing the way Soneji's stepmother once locked him in a basement as a child. Soneji also kills three people at New York's Penn Station with a cyanide-tipped knife and escapes into the subway tunnels.
At Lorton Prison, an inmate named Jamal Autry reveals that a prisoner named Shareef Thomas assaulted Soneji, and that Soneji now has HIV and is dying with nothing left to lose. Cross reconnects with Christine, who admits she has stopped being afraid, and they kiss for the first time. In New York, Cross works the Penn Station case with NYPD Detective Manning Goldman, theorizing that train tunnels symbolize the cellar of Soneji's abusive childhood. Cross also discovers that his own blood, stolen from a hospital blood bank, was deliberately planted on the Union Station rifle.
Soneji murders Goldman inside the detective's home. Cross suspects Soneji used Goldman's computer to locate Thomas, now hiding in a Brooklyn crackhouse. Cross infiltrates the crackhouse, but when Goldman's partner, Detective Carmine Groza, storms in prematurely with uniformed officers, Thomas opens fire. Cross kills Thomas in the shootout, losing their only link to Soneji. He suggests staging Thomas's survival at Bellevue Hospital to lure Soneji.
Meanwhile, FBI agent Thomas Pierce examines Mr. Smith's crime scenes alongside Interpol inspector Sondra Greenberg. In Paris, Smith accosts and abducts a young surgeon, Dr. Abel Sante, from the street. FBI agent Kyle Craig pressures Cross to join the Smith investigation and meet Pierce, but Cross refuses.
When Soneji infiltrates Bellevue disguised as a nurse, he finds Cross and Groza waiting. He hurls a firebomb and flees. A chase erupts through the hospital, onto a city bus where Soneji takes a baby hostage, and into Grand Central Station's underground tunnels. Soneji throws the baby to safety and attacks Cross. Cross shoots Soneji through the jaw, and a bomb in Soneji's pocket ignites. Soneji burns to death, warning: "You're going to die. You can't stop it from happening. I'm coming for you, even from the grave."
Cross returns home to a surprise celebration party, but in the early hours an intruder attacks him in his bedroom, beating him with a heavy weapon and shooting him twice. The attacker also beats Cross's grandmother, Nana Mama, and the children but does not kill anyone, screaming, "I told you there was no way to stop me!"
The narrative shifts to Pierce's first-person perspective as Kyle Craig assigns him to investigate the attack. Pierce finds Cross's charred detective shield in the cellar stove, left as a deliberate message. At the hospital, Pierce visits Cross, who is conscious but unresponsive, and privately thinks it might be better if Cross does not survive. Pierce and Sampson investigate Soneji's background in Princeton, New Jersey, uncovering evidence of Soneji's earliest kills at his grandfather's farm. Pierce then identifies Simon Conklin, Soneji's only childhood friend, as the likely attacker, finding incriminating evidence at Conklin's house. Pierce declares himself better than Cross.
The novel reveals its central twist. Cross, narrating again, addresses FBI agents at Quantico and announces that reports of his near-death were greatly exaggerated. Craig manufactured the hospital bulletins to lure Pierce into the investigation, believing Pierce's ego would drive him to expose himself. Cross presents the theory that Pierce is Mr. Smith. Years earlier, Pierce discovered his fiancée, Isabella Calais, was having an affair with a doctor named Martin Straw. Pierce murdered Isabella in their Cambridge, Massachusetts, apartment, impaling her heart on a spear: a confession embedded in his own name. He then created the Mr. Smith persona, committing a string of murders as ritualized self-punishment, re-enacting Isabella's death with each victim.
The FBI sets a trap at Conklin's house, but Pierce arrives first and forces a taped confession that Conklin attacked the Cross family on Soneji's orders. Pierce then reveals himself as Mr. Smith, performs a savage mutilation of Conklin, and escapes before agents can intervene. Cross decodes Pierce's murder pattern: The first letters of each victim's name, taken in order, spell "I MURDERED ISABELLA CALAIS." Cross realizes Pierce needs one final victim whose name begins with S, which could stand for Smith himself or for Dr. Martin Straw, Isabella's former lover.
The FBI sets a trap at Straw's home in Concord, Massachusetts, but Pierce intercepts their radio communications and flees. During a high-speed chase, Pierce fires at Cross and Sampson and screams, "I murdered Isabella Calais and I can't stop the killing." He abandons his car and vanishes into the woods.
Cross deduces that Pierce will return to the Cambridge apartment he shared with Isabella. Cross enters the bedroom alone and finds Pierce on the bed, his chest cut open by his own scalpel in a self-autopsy, making himself Mr. Smith's final victim. Cross tries to save him, but Pierce slashes Cross's palm. Sampson fires twice, killing Pierce.
Cross returns to his family and deepens his relationship with Christine. In an epilogue, Cross takes his family and Christine to Bermuda. After several idyllic days, Christine goes moped-shopping alone in Hamilton and does not return. At four in the morning, an anonymous caller directs Cross to check his e-mail. The message reads: "She's safe for now. We have her." The novel ends on this cliffhanger, with Cross facing an unknown threat.