The hosts bring fine form into this encounter, but have struggled in the Coppa for decades, while La Dea are seeking their first title in 61 years.
Match preview
A fifth straight win at home saw Milan make the perfect start to the new year when they beat Cagliari 4-1 in the last 16 of the Coppa.
That fine beginning to 2024 continued with a 3-0 win at Empoli in Serie A on Sunday afternoon, which keeps Stefano Pioli's side third.
While still a hefty distance off their local rivals Inter Milan at the top of the table, Milan were able to close the gap to nine points, with half of the season now played.
Despite the stature of Milan, both domestically and in Europe, they have rather surprisingly never been a strong outfit in this competition.
Their only Coppa title in almost half a century came in back in 2003, but they did come up just short in 2016 and 2018, losing finals to Juventus on both occasions.
After seven straight home games against Atalanta without a win, Milan have now recorded back-to-back 2-0 victories at San Siro over their upcoming opponents, and a third will seal their spot in the semi-finals.
The Rossoneri were beaten in dramatic circumstances when the sides met in Serie A last month though, with Luis Muriel's 95th-minute winner earning Atalanta all three points in a 3-2 success.
The visitors come into this game on the back of a respectable result away to another of Italy's giants, after La Dea drew 1-1 at the Stadio Olimpico against Roma on Sunday.
Manager Gian Piero Gasperini was satisfied with the result, but rued his side's missed chances in the capital, as Atalanta sit sixth, three points shy of the top four.
It was another away game without a win too, as Gasperini has seen his side win just one out of six on the road domestically.
After beating Sassuolo 3-1 in the previous round, that worrying away form could see them crash out at this stage for the third successive season, after being eliminated by Fiorentina and Inter Milan in the past two years.
Atalanta, like Milan, have lost two Coppa finals themselves in recent years, falling at the final hurdle in both 2019 and 2021.
AC Milan Coppa Italia form:
W
AC Milan form (all competitions):
W
W
D
W
W
W
Atalanta BC Coppa Italia form:
W
Atalanta BC form (all competitions):
W
W
L
W
W
D
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Team News
Milan will now be without Samu Chukwueze and Ismael Bennacer for the next few weeks, with both players away at the Africa Cup of Nations.
Defence is where Milan's big problems still lie though, as Fikayo Tomori, Malick Thiaw and Pierre Kalulu are all out injured.
Simon Kjaer and Jan-Carlo Simic are their only two current options at centre-back, but the ultra-offensive Theo Hernandez has been forced into the centre to cover for the mounting injuries.
Tommaso Pobega and Noah Okafor will also both miss out, but that could give 19-year-old Chaka Traore another opportunity to start, after scoring in both of Milan's fixtures in 2024 so far.
Atalanta also have a key player away at AFCON, with top scorer Ademola Lookman joining up with the Nigeria squad.
Aleksei Miranchuk has grasped the opportunity of more game time in Lookman's absence and been Atalanta's best player in the last two games.
Away from league action though, that could see Gasperini give Muriel and Gianluca Scamacca starts in attack, while Mario Pasalic and Davide Zappacosta may also come into the team.
Gasperini is expected to make a change between the sticks, with Juan Musso likely to come in for Marco Carnesecchi.
On the injury front, Hans Hateboer, Rafael Toloi and El Bilal Toure are all currently sidelined for the visitors.
AC Milan possible starting lineup:
Maignan; Calabria, Kjaer, Hernandez, Florenzi; Reijnders, Adli, Loftus-Cheek; Pulisic, Jovic, Traore
Atalanta BC possible starting lineup:
Musso; Scalvini, Djimsiti, Kolasinac; Zappacosta, De Roon, Pasalic, Koopmeiners, Ruggeri; Muriel, Scamacca
We say: AC Milan 2-1 Atalanta BC
Milan have been exceptional at home over the past few months, and are favourites to progress in what could be a very open game at San Siro.