Pirlo appeared in over 280 matches for Milan during his time with the club, but he will be returning with a Juventus side that sits one point back of his former team with a game in hand.
Juve has gone 23 matches in Serie A this season without a defeat, but Saturday's trip to Milan figures to provide the club with its biggest test.
Despite its unbeaten record, Antonio Conte's side has drawn 10 games this season, including three in its last six, while Milan has won four of six and can put a bit of space between itself and Juve with a win.
However, three points will be a little tougher for Milan to achieve on Saturday without the services of striker Zlatan Ibrahimovic, who will be serving the final game of a three-match ban.
The Swede tried to get the ban reduced to two games but was turned down, meaning manager Massimiliano Allegri will be without his leading scorer, who has netted 15 goals so far this term.
Allegri's attacking options will be further diminished by the absence of both Kevin-Prince Boateng and Maxi Lopez, who are out through injury, while Alexandre Pato is expected to make his first league appearance since mid- January.
Udinese will try to snap a poor spell of play that has seen the club win one of its last five games when the team visits bottom-half side Bologna, while Lazio, which is level on 42 points with Udinese in third place, hosts Fiorentina.
Roma continues to chase a place in the Champions League with a trip to Atalanta up next on Sunday following a 1-0 win over Parma last time out.
Napoli won its third straight game in all competitions by beating Chelsea 3-1 on Tuesday in the Champions League and hosts a struggling Inter Milan outfit that has lost four straight, including a 1-0 defeat at Marseille in midweek.
Genoa and Parma square off at the Luigi Ferraris Stadium in the other match on Saturday, while the rest of Sunday's schedule includes Lecce visiting Cagliari, second-from-the-bottom Novara meeting Catania, Chievo entertaining last-place Cesena and Palermo clashing with Siena, which sits two points above the drop zone.