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Edson Barboza was expected to face Evan Dunham on May 26, 2012, at UFC 146, but Dunham dropped out of the bout due to injury and was replaced by returning veteran Jamie Varner. Barboza entered the fight as a near 5-to-1 favorite over Varner, making this one of the bigger upsets in recent memory. Coming off a KO of the year candidate versus Terry Etim, many expected Barboza to be the first to knock out Varner, who came into the bout as a late replacement.
Barboza got off to a strong start, looking to chop Varner down with leg kicks, but the fight shifted when Varner caught a kick and took him down, scoring ground strikes. Barboza got back to his feet but Varner staggered him with a straight right hand. He dropped him with another right and dropped a series of hammerfists over his fallen opponent until ref Steve Mazzagatti had seen enough. The former WEC champion immediately ran to a camera and mouthed the words, "I'm back."
Barboza suffered his first professional MMA loss via Knockout in the first round.