Juventus, who go into Saturday's action with next Tuesday's Champions League quarter-final, first-leg game against the Spanish champions in Turin looming, are just two points ahead of Napoli with nine matches left this season.
After a recent dip in form as they pursue a first Scudetto since 1990, Maurizio Sarri's Napoli got back to winning ways against Genoa before the international break.
And Gennaro Gattuso's AC Milan — in sixth with a game in hand — will be determined to take away three points from Turin as they look to continue their push for Champions League football next season.
Milan are on a 10-game unbeaten streak, including eight wins, a tally which has seen Gattuso, who took over in November, move closer to penning a permanent contract with the club.
The former midfielder was the match-winner the last time Milan won at Juventus back in March 2011.
"Winning in this game will be important, not only for Serie A but to give us a boost in the Champions League," said Juventus defender Andrea Barzagli. "The two upcoming challenges will represent a crucial moment in our season, as they will both be very decisive. The biggest mistake we could make would be to think about Real Madrid. The match against Milan is very important, we have big objectives that we want to achieve and it will be a very difficult game."
Juventus' run of 12 straight league wins was ended last time out against SPAL, but they remain unbeaten in 24 matches going back to November 19.
And Massimiliano Allegri's side can set a new all-time league record for time without conceding a goal if Milan do not score before the 44th minute.
A win would also give goalkeeping great Gianluigi Buffon his 300th victory with the club.
Juventus won their last Serie A meeting against Milan 2-0 at the San Siro last Novmeber in one of the final games for Gattuso's predecessor Vincenzo Montella.
And Barzagli conceded: "To be honest, I was surprised at how they started their season, but now they are going strong and you can also see the influence that Gattuso has had, so we have to give maximum attention."
Napoli, meanwhile, may not have it all their own way at Sassuolo having failed to come away with a win in their last two trips to the Mapei Stadium.
Sassuolo are three points above the drop zone but boosted by their first win since before Christmas at Udinese last time out.
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