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Mikkelsen began his career in the late 1990s and quickly won critical and audience acclaim with his outstanding performances. His filmography includes:

- "Trip to Broadway" (2002): In this film, he played the role of a famous Danish director who is trying to recreate his life on Broadway.

- "King Arthur" (2004): In this historical epic, he played the role of the main antagonist, the sinister knight.

- "Casino Royale" (2006): In this film about the adventures of James Bond, he played the role of Le Chiffre, one of the most memorable villains in franchise history.

Despite his success in Hollywood, Mikkelsen remains true to his roots and often starred in Danish films, continuing to delight the audience with his outstanding performances. His talent and dedication to art make him one of the most sought-after and respected actors of his generation.