This story takes place over the course of a few days. In the novel, the story takes place over the course of around two years. Also, in the book, Alex Cross is 38 years old with two kids, where as in the film, he is in his mid to late fifties.
The scene where Alex Cross pays the kidnapper by throwing the thermos containing the ransom from the window of a transit train is taken from James Patterson's novel "Roses Are Red", which starred Alex Cross investigating another of his "best enemies", Kyle Craig, a.k.a. "The Mastermind".
In the book, the Secret Service is protecting the young boy from the school, and Alex Cross is forced onto the case, not drawn in. Also, there is no female partner, like in the beginning of the movie, but a partner and best friend since he was nine.
The film is almost unrecognizable from the novel on which it's based, aside from the main characters Alex Cross, Soneji, and Jezzie, all of whom mostly resemble their novel counterparts in name only. It is almost a brand new story.
Michael Moriarty plays the father of the kidnapped girl "Megan". Moriarty previously played the part of the stepfather (Hull Barret) of a girl also named "Megan" in Pale Rider (1985), with Clint Eastwood.
The trivia items below may give away important plot points.
Substantial changes were made from the book. For example, the Gary Soneji story arc continues for four books, and he dies under entirely different circumstances. Also, there are two kids kidnapped in the book, one of which dies in the process, which results in Jezzie Flannigan's execution via lethal injection.
In the previous film, Kiss the Girls (1997), Cary Elwes plays a Durham police detective working the case with Cross, but is ultimately found to be the killer. In this film, Monica Potter plays a secret service agent working the case with Cross, but is ultimately discovered to be one of the kidnappers as well as a killer. Elwes and Potter would later co-star as husband and wife in Saw (2004).