In 1999, Mikkelsen had a leading role as Lenny, a shy film expert who suffers from avoidant personality disorder, opposite Kim Bodnia in Refn's Bleeder (1999). He played marginalized, often comic roles in popular Danish films. Mikkelsen made his film debut in 1996 as a drug dealer in Nicolas Winding Refn's internationally successful film Pusher, which spawned two sequels. He was a professional dancer for almost a decade until he left it behind to study drama at the Århus Theatre School in 1996, embarking on a career in acting. During his dancing career, Mikkelsen met choreographer Hanne Jacobsen, whom he married in 2000. In his youth, he trained as a gymnast, wanting to pursue athletics, but then studied dancing at the Balettakademien (ballet academy) in Gothenburg where he also became fluent in Swedish.

He and his older brother, actor Lars Mikkelsen, were raised in the Nørrebro district. Mikkelsen was born on 22 November 1965 in the Østerbro district of Copenhagen, Denmark, the son of mother Bente (Christiansen) Mikkelsen and father Henning Dittmann Mikkelsen, a cab driver. Scott of The New York Times remarked that in the Hollywood scene, Mikkelsen has 'become a reliable character actor with an intriguing mug' but stated that on the domestic front 'he is something else: a star, an axiom, a face of the resurgent Danish cinema'. Hannibal Lecter in the television series Hannibal (2013–2015), Kaecilius in Marvel's Doctor Strange (2016), Galen Erso in Lucasfilm's Rogue One (2016), Cliff Unger in Hideo Kojima's video game Death Stranding (2019), his BAFTA-nominated role as Martin in Another Round (2020), Gellert Grindelwald in Fantastic Beasts: The Secrets of Dumbledore (2022) and Jürgen Voller in Indiana Jones and the Dial of Destiny (2023). His other roles include Igor Stravinsky in Coco Chanel & Igor Stravinsky (2008), Johann Friedrich Struensee in A Royal Affair (2012), his Cannes Film Festival Best Actor Award-winning performance as Lucas in the Danish film The Hunt (2012), Dr. Mikkelsen achieved worldwide recognition for playing the main antagonist Le Chiffre in the twenty-first James Bond film, Casino Royale (2006). He rose to fame in Denmark as an actor for his roles such as Tonny in the first two films of the Pusher film trilogy (1996, 2004), Detective Sergeant Allan Fischer in the television series Rejseholdet (2000–2004), Niels in Open Hearts (2002), Svend in The Green Butchers (2003), Ivan in Adam's Apples (2005) and Jacob Petersen in After the Wedding (2006). Mads Dittmann Mikkelsen ( Danish: ⓘ born 22 November 1965) is a Danish actor and former gymnast and dancer. Knight of the Order of the Arts and Letters.

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