The book’s plot revolves around the attempts of Harvard symbology professor Robert Langdon to prevent an ancient secret society called the Illuminati from destroying Vatican City with a powerful new weapon involving antimatter. Antimatter research was headed by a physicst at CERN, the European Organization for Nuclear Research. The physicist is murdered, and the canister containing the antimatter falls into the hands of the Illuminati. In the meantime, the pope dies, leading to a contest for succession within the Vatican. This becomes complicated when four cardinals — including one seen as a frontrunner to be the next pope — are kidnapped by the Illuminati. Langdon and CERN researcher Vetra Vittoria must follow a series of ancient clues to find a secret altar before the stolen antimatter explodes and levels Vatican City.
The murdered scientist is named Silvano Bentigolio in the book, and is merely Vittoria’s colleague; in the movie, the character is named Leonardo Vetra, and is her adoptive father. CERN director Maximillian Kohler is a recurring character in the book, but is completely absent from the film. The film character of Camerlengo Patrick McKenna (played by Ewan McGregor) is, in the book, an Italian named Carlo Ventresca. Likewise, the novel’s Cardinal Mortati has been renamed Cardinal Strauss in the film. In the book, a man named Olivetti is the head of the Swiss guard; in the film, a character called Richter heads the Swiss guard and is a new character created for the movie who's a combination of Olivetti and Kohler.
The jet that whisks Langdon from Harvard to Geneva at Mach 15 in the book doesn't appear in the movie. The assassin in the novel is a Middle Eastern descendent of the original Hassassin with Illuminati beliefs; the film version's assassin is a European hit man motivated solely by money. In the book, Langdon steals a car by threatening the driver to get to the final altar in time; in the film, he's escorted by police officers. In addition, the novel’s subplot involving two BBC news reporters is entirely absent from the movie. Perhaps the largest plot difference, however, is the relationship between Langdon and Vetra, which is romantic in the book, but platonic in the movie.
The book makes repeated reference to Vetra’s short pants, which are considered unsuitable for a woman within the Vatican. In the film, she wears long pants. When Langdon and Vetra kill the assassin in the book, they push him off a balcony; in the movie, he dies in a car bomb that was meant to murder Camerlengo McKenna. The book also details the Illuminati Diamond, the branding iron that combines all four elements into one shape. In the film, the brand is two key crosses.