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While the film is an homage to the 1930s and '40s Universal Monster horror films, the inclusion of Mr. Hyde is an oddity, as he was never one of the Universal Monster roster. Instead, the films based on Hyde during that time were made for Universal's rival MGM. However, in 1953, Universal did feature the monster in the comedy Abbott and Costello Meet Dr. Jekyll and Mr. Hyde (1953).

Stephen Sommers wanted Kate Beckinsale for the role of Anna, but feared it was too similar in tone to the vampire/werewolf film Underworld (2003) which she was shooting at the time, and he didn't ask her. Eventually her agent got Sommers to send the script and Beckinsale immediately signed on.

Before David Wenham was cast as Carl, Paul Hogan was reportedly considered for the role.

The Netherlands audience awarded Van Helsing (2004) with the 'TV Krant Filmposter Award' of 2004.

A spin-off TV series was pitched to NBC. To have been called "Transylvania", it was to have featured a wild-west sheriff taken to Europe to battle monsters, with occasional guest appearances by Hugh Jackman as Gabriel Van Helsing. The series idea was stillborn, partly because makeup, effects, and location shooting in Romania would have been too expensive, and partly because the film's opening weekend box office was far below expectations (which also doomed a proposed sequel to the film).

Elena Anaya (Aleera) was originally featured in the masquerade ball but her scenes were deleted.

The scene where Van Helsing, Carl and Frankenstein's creature meet Aleera in Budapest was Elena Anaya's first day on set.

The second-to-last scene of X2 (2003) (Cyclops, Wolverine, and Professor X discussing Jean Grey) was filmed while Hugh Jackman had a day off from this movie.

The last scene shot for actor Will Kemp was actually his death scene. It was filmed in Griffith Park in Los Angeles, California. In the scene he is to lay against a rock. What the crew did not know was that there were a lot of spiders in the area and when Kemp's scene was finally completed, he went home with many spider bites on his back and arms.

The Transylvanian town built for this movie is to be the basis for a TV series. According to the producers, it was too good to just tear down.

Silvia Colloca is terrified of heights and joked in an interview that she wasn't acting for the scene where Verona and Aleera are hanging upside down.

Cans delivering the film to theaters were labeled "The Vatican Detective".

The DVD sales was $65 million in the first week in North American, more than half the revenue from theater runs.

This is the first movie, other than the Lord of the Rings films, to use the MASSIVE software program developed for the Lord of the Rings trilogy.

Shuler Hensley reprised his role of Frankenstein's Monster in Mel Brooks's stage adaptation of Young Frankenstein (1974). Costarring Roger Bart as Dr. Frederick Frankenstein, the play opened at the Hilton Theater, New York City on November 8, 2007. It closed on January 4, 2009 after 29 previews and 485 performances.

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