The CERN scientist who gets murdered in the beginning of the film is called Silvano Bentivoglio, who is Vittoria Vetra's colleague only. In the book, his name is Leonardo Vetra, and he is both Vittoria's colleague and adoptive father. The book opens with the murderer branding Vetra with the Illuminati ambigram in the chest.
In the book, there is no scene where the Large Hadron Collider is activated; the antimatter has already been created and stored.
CERN director Maximilian Kohler, a sickly and wheelchair-bound man, is completely absent in the movie. In the book, he is the one who calls Langdon to the CERN complex in Geneva and shows him the dead body with the Illuminati symbol burnt into it. Vittoria later joins them and confesses that she and her father had secretly started to produce antimatter, without Kohler knowing. Kohler eventually goes into a coughing fit and gets hospitalized.
The plane that goes Mach 15 is completely absent in the film. It's the plane that takes Langdon from Harvard University to Geneva, and brings Langdon and Vittoria to Vatican City.
Vittoria wears short pants in the novel which is frowned upon in the Vatican. In the film she wears long pants.
Camerlengo Patrick McKenna is called Carlo Ventresca in the novel, where he is an Italian. Likewise, Cardinal Mortati in the novel is Cardinal Strauss in the movie. Father Simeon appears in the movie but not in the book.
In the book, Olivetti is the head of the Swiss Guard. In the movie, Olivetti is only head of the Vatican Police and much kinder. The character Richter was created especially for the movie, he is the head of the Swiss Guard and acts more like how Olivetti did in the novel.
In the novel, the assassin is Middle Eastern and calls himself 'the descendant of the Hassassin'. In the movie he's European. The Hassassin is an Illuminati believer in the novel. He also has a craving for sex with women. In the movie both of these are absent: he is more of a professional, with strong ethics, only caring about money. In the novel he delivers the threat to the Camerlengo, Olivetti, Vittoria and Robert personally over the phone, announcing the Illuminati's revenge for 'La Purga'.
The Hassassin's contractor's name is Janus in the novel. In the movie, the name is only mentioned once and barely noticeable.
Langdon is alone in the Vatican Archives in the novel when he gets locked in by the power going out. As he has no gun, he breaks the glass by just crashing the bookshelf into it. Robert suspects Captain Rocher, Olivetti's subordinate who is absent from the film, of trying to kill him.
The FIRE death is a little different. In the novel, Olivetti enters the church first. When he does not repond, Robert and Vittoria enter. They find Olivetti with a broken neck. They try to save the cardinal, who is completely naked, but the Hassassin tries to kill Robert, who hides under a sarcophagus and crushes the Hassassin's arm under it. The Hassassin kidnaps Vittoria and leaves, thinking Robert will suffocate under the sarcophagus. Robert is freed just in time by firemen. He steals a car by 'threatening' to shoot the driver to get to the fourth Illuminati altar by himself. In the movie he is escorted by Police Officers.
When arriving alone at the Four Rivers fountain in the novel, Robert notices the Hassassin's van is already parked next to it, waiting for the right time. He enters the fountain on the other side and holds the Hassassin at gunpoint. However, the Hassassin quickly throws cardinal Baggia's naked body into the fountain and gets the jump on Robert. Robert wounds him in the foot, but a fight ensues, in which Robert is held under water. He grabs a water hose and fakes drowning until the Hassassin leaves him for death. Robert tries to revive cardinal Baggia, but does not succeed. He derives the location of the Illuminati church himself from a clue in the fountain (instead of cardinal Baggia telling him as in the movie).
Langdon makes his way to the Castle of Angels alone, only to find out that the door is locked and the wall is too high to climb. He enlists the help of the driver of a nearby newsvan to help him over the wall. Inside, he finds the Hassassin trying to rape Vittoria to celebrate his victory of killing all four Cardinals. Another fight with the Hassassin ensues. Both Vetra and Langdon are the ones who kill the Hassassin by pushing him off the balcony (not a car bomb that is rigged to blow by the Camerlengo).
A complete subplot with two BBC news reporters is completely absent in the film. The Hassassin calls them and informs them of the killings, causing them to broadcast the news of the kidnapped cardinals live over the world. In the book, the Camerlengo orders them inside the Sistine Chapel and allows them to broadcast his statement to the cardinals live to the world. This speech is longer and much more elaborate in the book, and includes a lengthy statement about the church having to "surrender to science", and the sentence "religion is flawed, but only because man is flawed" (said in the movie by Cardinal Strauss at the end).
Maximilian Kohler is the one in the book who finds and reads Vetra's diaries, and then goes out to confront the Camerlengo (not Richter like in the movie). When Robert and Vittoria learn of his arrival, their initial thought is that Kohler is the Illumnati leader. Captain Rocher is the one who knows the truth and therefore allows Kohler into the Camerlengo's office. When Kohler and Rocher (Father Simeon in the movie) are shot down, Kohler had video taped the whole Camerlengo conversation and gives it to Langdon upon death, asking him to "Give it to the media."
The Illuminati Diamond, the final brand iron which combines all four elements into one shape, and which is used on the Camerlengo, is completely absent from the film. The final brand in the movie consists of two key crosses. This image is what provides a clue to Robert as to where the antimatter cannister is hidden (Saint Peter's tomb). However, in the novel, the Camerlengo suddenly receives a vision from God, leading him to Saint Peter's tomb.
In the book, both Langdon and the Camerlengo enter the helicopter with the antimatter. Robert is under the impression that the Camerlengo plans to throw the antimatter out in time so it will explode in mid-air. However, the Camerlengo locks the antimatter into a cargo box and jumps out of the helicopter with a parachute, saying to Robert that "it wasn't supposed to happen this way". Langdon manages to escape the exploding helicopter by grabbing a windshield cover and jumping out. The cover slows his descent just enough for him to survive a big splash into the Tiber river. He is rescued by personnel of a small nearby hospital. There he finds out what was on the video camera he had received from Kohler.
Langdon returns to the Sistine Chapel and shows the video of Kohler and the Camerlengo in the novel to all the Cardinals. The video only has the Camerlengo confessing the murder of Leonardo Vetra; after this, the Camerlengo confesses his anger over the late Pope's decision to stimulate Vetra to go public with his antimatter work, and gives a lengthy justification of all his doings, which include handing the confiscated Illuminati brands to the Hassassin, ordering the deaths of the Preferiti, and murdering the Pope. Cardinal Mortati then reveals that the Camerlengo was, in fact, the late Pope's actual son, through artificial insemination. The Pope had fallen in love with a nun and wanted to keep his vow of celibacy to the Church, so the nun found out about the artificial insemination and they both stayed virgins. The Pope had tried to tell the Camerlengo but he had stormed out angrily after hearing the Pope confess that he had fathered a child. This - coupled alongside everything he has done - is what drives the Camerlengo to suicide. Only in the book, the Camerlengo immolates himself in front of everyone in St. Peter's Square.
Cardinal Mortati (Cardinal Strauss in the film) collects the Camerlengo's ashes in an urn, which he places into the late Pope's tomb. He himself gets elected pope in the novel. It is also revealed that the Camerlengo was actually rightfully elected Pope right before Mortati through the "acclamation by admiration" (mentioned in the movie), for just a few minutes though.
Langdon is given the Illuminati Diamond in the novel at the end by the new pope. Langdon and Vittoria fall for each other and end up having sex with each other. Their love relationship is absent in the movie.