Between them, the two clubs have won Europe's premier club competition on 11 occasions and they meet at the Amsterdam Arena on Tuesday.
De Boer, whose men were beaten 4-0 by Barcelona in their opening game, feels that the Italian striker could make all the difference for the Milan.
Balotelli has three goals in four Serie A games this season and the former Netherlands international likened him to Barcelona forward Lionel Messi.
"Messi is a player that can decide a match and with Balotelli it's the same," De Boer said.
"Balotelli is a fantastic player and next to him are players who can also make the difference. Milan have three very strong forwards and and a good midfield."
Despite their defeat at the hands of the Spanish champions, De Boer backed his side to pose a threat against Massimiliano Allegri's men.
"I am positive, I think that if we remain focused for 90 minutes we can get a good result here," said De Boer.
"We will go into the match with a positive attitude. We do not have a team that can hang back and play on the counter but they do.
"The most important thing is that we try to take three points."
Ajax come into the game off the back of mixed domestic form, having followed up their defeat against Barcelona with a 4-0 loss to PSV Eindhoven.
The Eredivisie champions then edged Volendam 4-2 in the KNVB Cup before seeing off Go Ahead Eagles 6-0 on Saturday.
