The 34-year-old Dutch midfielder played for Real from 1996-1999, helping the Spanish side win Europe's elite club competition in 1998 before going on to win two more Champions League titles with Milan in 2003 and 2007.
"I think it's going to be a nice match," Seedorf said at a news conference in Madrid on Monday.
He added that Real's coach, Jose Mourinho, who left Milan's city rivals Inter for Madrid at the end of last season, already appeared to have made his mark on the club.
"I have seen Mourinho's team play and I think you can already see the hand of the coach," Seedorf said.
Nine-times champions Real are one of six teams seeking on Tuesday to maintain their perfect record in this season's competition. Real beat Ajax Amsterdam and Auxerre in their opening two games.
Milan, the seven-times winners, were held to a 1-1 draw in Amsterdam at the end of September.
English Premier League sides Chelsea and Arsenal won their opening two matches, as did Bundesliga club Bayern Munich, Russia's Spartak Moscow and Ukrainian side Shakhtar Donetsk.
Chelsea face Spartak at the stadium where they lost the 2008 final to Manchester United, Arsenal host Shakhtar, and Bayern play CFR Cluj of Romania.
Chelsea coach Carlo Ancelotti said he did not think his captain, John Terry, would be affected by returning to the scene of his crucial penalty miss in the penalty shootout against United in 2008.
"John Terry has great experience so I think what happened two years ago has no effect on him," Ancelotti said. "Everyone knows in football you can sometimes lose the games."
