Holyfield, 46, has agreed to a bout with Russia's WBA champion Nikolai Valuev on Dec. 20 in Zurich, the BBC said.
Analysts say the American's chances against the 7-foot Valuev are slim to none because Valuev will have a seven-inch reach advantage and weighs at least 100 pounds more than Holyfield.
"I'm taking this fight very seriously," said the 35-year-old Valuev, a 1984 Olympic bronze medal winner. "Holyfield is a strong opponent, and 10 years ago I would not have dreamed of getting into the ring with this champion."
Holyfield has not fought since losing a unanimous decision on Oct. 13, 2007 to then-WBO champion Sultan Ibragimov.
His career record is 49-9-2, but since 2001, he has won only five of 11 fights.