Atalanta play their first ever Champions League Round of 16 with Papu Gomez, Josip Ilicic and Mario Pasalic against a decimated Valencia.
The first leg kicks off at San Siro at 20.00 GMT.
This is the debut Champions League tournament for the club from Bergamo, yet they went through the group stage, finishing second only to Manchester City, and will feel they have a good chance of reaching the quarter-finals too.
Gian Piero Gasperini has a full squad to choose from and the only real doubt in his mind was between Duvan Zapata as the centre of the trident attack, or Ilicic as a False 9 to leave no reference points for the Valencia defenders.
Duvan Zapata is still working on full fitness after three months out with a thigh tear, so Ilicic gets the nod with support from Papu Gomez in a more advanced role than usual, plus Pasalic, bringing Remo Freuler into midfield.
This system was used several times during the group stage, when Duvan Zapata was out of action, as Luis Muriel is seen more as an option to come off the bench and take on tired opponents.
Valencia, on the other hand, have an injury crisis and have made the trip without numerous players, including suspended Gabriel Paulista and chickenpox sufferer Alessandro Florenzi.
Francis Coquelin, Kang-in Lee, Rodrigo, Ezequiel Garay, Cristiano Piccini and Manu Vallejo are also unavailable, with Kevin Gameiro, Denis Cheryshev and goalkeeper Jasper Cillessen not fully fit.
Valencia have some familiar faces, such as former Inter midfielder Geoffrey Kondogbia.
Maxi Gomez leads the way with Goncalo Guedes in support, but the biggest changes are at the back.
Eliaquim Mangala and former Olympique Lyonnais centre-back Mouctar Diakhaby can be unpredictable and are not accustomed to working together.
Gabriel Paulista and Garay were usually the first choice central defenders, while Rodrigo is a huge loss, having scored two and assisted two in his five Champions League games this season.
The teams need to be careful, as Josip Ilicic, Marten de Roon, Berat Djimsiti and Daniel Wass are one yellow card away from suspension for the second leg.
This is the first time these sides have ever crossed paths, but Valencia have a poor record on Italian soil, winning only one of their eight Champions League games here, drawing two and losing the other five.
That was a 1-0 group phase result at Roma in 2002-03.
Los Che also failed to find the net in six of those eight previous matches played in Italy.
Atalanta: Gollini; Toloi, Palomino, Djimsiti; Hateboer, De Roon, Freuler, Gosens; Pasalic; Ilicic, Gomez
Atalanta bench: Sportiello, Caldara, Tameze, Muriel, Malinovskyi, Castagne, Duvan Zapata
Valencia: Domenech; Wass, Diakhaby, Mangala, Gayà; Ferran Torres, Parejo, Kondogbia, Soler; Maxi Gomez, Goncalo Guedes
Valencia bench: Cillessen, Thierry Correia, Jaume Costa, Gameiro, Cheryshev, Ruben Sobrino, Gutierrez
Ref: Oliver (ENG)
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