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In 1982, an extraterrestrial spaceship is discovered beneath the Antarctic ice by a Norwegian research team: Edvard (Trond Espen Seim), Jonas (Kristofer Hivju), Olav (Jan Gunnar Røise), Karl (Carsten Bjørnlund), Juliette (Kim Bubbs), Lars (Jørgen Langhelle), Henrik (Jo Adrian Haavind), Colin (Jonathan Lloyd Walker), and Peder (Stig Henrik Hoff). Paleontologist Kate Lloyd (Mary Elizabeth Winstead) is recruited by Dr. Sander Halvorson (Ulrich Thomsen) and his assistant Adam Finch (Eric Christian Olsen) to investigate the team's discovery. After viewing the ship, Kate, Sander, and Adam are informed that the group has also discovered a survivor of the crashed ship buried in the ice.
The alien is transported to the Norwegian base in a block of ice. Sander orders the retrieval of a tissue sample from the creature against Kate's warnings. That evening while the team celebrate their find, helicopter co-pilot Derek (Adewale Akinnuoye-Agbaje) observes the alien burst free from the ice and escape the base. The alerted team search for the creature and discover Lars's dog mutilated. Olav and Henrik find the alien which kills Henrik. The rest of the group arrive and set fire to the alien. An autopsy of the scorched alien corpse reveals that its cells are still alive and are consuming and imitating Henrik's own.
Derek, fellow pilots Carter (Joel Edgerton) and Griggs (Paul Braunstein), and Olav prepare to leave the base by helicopter to seek help. In the base Kate discovers bloody, metal, tooth fillings near a blood-soaked shower. Kate runs outside and flags down the helicopter, but when it attempts to land Griggs transforms into the alien and attacks the crew, causing the vehicle to crash land in the mountains; the crew presumed lost. When Kate returns to the shower, she finds the blood has been removed. The base team agree to leave to find help but Kate confronts them with her theory that the "Thing" is capable of imitating them and has likely already done so. The team dismiss her claims, but Juliette confesses that she saw Colin leaving the bloodied shower. Juliette takes Kate to secure the vehicle keys to prevent the others leaving. While Kate searches, Juliette transforms into the Thing and attacks Kate. Kate flees, running by Karl whom the creature consumes instead. Lars arrives with a flamethrower and burns the Thing.
Carter and Derek return to the base, but the team refuse to believe that they could have survived the crash. Kate convinces them that Carter and Derek be isolated until a test can be prepared to check if they are still human. Adam and Sander develop a test, but their lab is destroyed in an apparent act of sabotage when both men momentarily leave. Kate proposes another method of eliminating some of the team as the Thing: Believing it cannot imitate inorganic material she inspects the team and singles out those without metal fillings: Sander, Edvard, Adam, and Colin. Lars and Jonas go to retrieve Carter and Derek, but discover they have broken out of isolation. As Lars leans inside a building in search of the pair, he is grabbed and pulled inside.
Jonas returns to Kate and Peder, begging for help. The group hear Carter and Derek breaking into the building and rush to intercept them. Edvard pressures Peder to burn both of them. Peder takes aim, but Derek shoots him multiple times, killing Peder and rupturing his flamethrower's fuel tank. The fuel ignites causing an explosion that knocks Edvard unconscious. While he is being carried for treatment, Edvard transforms into the Thing, infecting Jonas and killing Derek before assimilating Adam. Sander and Colin run out of the room while Kate torches the infected Jonas and Derek before she and Carter pursue the Thing. While the pair search, Sander is found and infected by the Thing. After the pair separate, the Thing corners Carter in the kitchen but Kate arrives and burns it to death before it can attack him. Kate and Carter observe Sander drive off into the blizzard and give pursuit in the remaining vehicle. When Kate questions Carter about what he and Derek did with Lars, he reponds "We didn't kill him."
They arrive at the now-active spaceship. Kate falls into ship and is confronted by the Sanders-Thing. She destroys it with an explosive grenade with the ensuing damage deactivating the ship. As Kate and Carter return to their vehicle Kate realizes that Carter is a Thing as he is no longer wearing an earring and Carter, when prompted on the issue, indicates the incorrect ear on which it was worn. Kate burns Carter and then retreats to her snowcat; she stares blankly out of the window.
The following morning helicopter pilot Matias arrives at the base. Colin is shown to have retreated into the radio room and committed suicide. Lars appears and shoots at Matias, ordering him to show his fillings to prove he is human. The Thing, in the form of Lars's deceased dog, escapes from the building and runs away. Lars and Matias give chase in the helicopter.