This story has been corrected. Read below
Bovada, as part of its NFL Player Props, believes the two will either shake hands or hug after the game. As of 11 p.m. ET Friday night, the line was minus-500 that they do and plus-300 that they don't.
The website says the handshake or hug must be clearly seen on TV for the bet to be final.
ESPN.com previously reported that the bets were being taken in Las Vegas.
The two coaches were at the center of a handshake controversy last year when Harbaugh gave an overenthusiastic handshake and pat on the back to Schwartz after the Niners ended the Lions' perfect start to the season in Week 6.
Schwartz took issue and the two had to be separated after San Francisco's 25-19 victory at Ford Field on Oct. 16. Harbaugh labeled the incident as a "mini controversy" and "completely irrelevant," and Schwartz said this week that the incident is "long in the past."
Information from The Associated Press was used in this report.
A Sept. 14 story on ESPN.com incorrectly reported that bets were being taken in Las Vegas on whether a handshake would occur between Detroit Lions coach Jim Schwartz and San Francisco 49ers coach Jim Harbaugh. The bets are being taken at Bovada, an online, offshore sports book.