Both teams are still within a shout of qualifying for the knockout phases, with the home side on six points and Atalanta on four.
The Ukrainian champions head into this game in the box seat knowing that just a draw over Atalanta, along with Dinamo Zagreb failing to beat Manchester City, would guarantee their place in the knockouts.
Unlike Atalanta, Shakhtar are not strangers to this competition and possess an impressive amount of pedigree - especially in home games.
For some time, Shakhtar have successfully pursued a transfer policy that places strong emphasis on signing Brazilian players, with five included in the starting XI against City.
This mixture of Brazilian fluidity and Ukrainian muscle, as Atalanta will discover, serves as a particularly well-rehearsed and dangerous combination in the Champions League.
That said, Atalanta will head into this game with a singular, driven mindset, knowing that a victory is the only thing capable of taking them into the knockout phases.
Previously a team that dwelled in the mid-table region, Atalanta's third place finish in Serie A last season stemmed from several years of good work under manager Gian Piero Gasperini, who guided the club to fourth during his first campaign in charge.
Playing with a 3-4-3 system, Atalanta press teams hard from the front and make the game a pacy, open affair whereby the Italian side looks to break into the final third with its wing backs at the forefront of attacks.
This style has helped them stand out in Serie A, although this has failed to translate to results in Europe, with Atalanta losing their opening three games in poor fashion.
However, a 1-1 draw with City and a win over Zagreb last time out has laid the platform for a potentially historic victory in eastern Europe this week.
Recent Shakhtar Donetsk form: LWDDD
Recent Shakhtar Donetsk form (all competitions): DWWDDW
Recent Atalanta form: LLLDW
Recent Atalanta form (all competitions): DDLWWW
Shakhtar head into this game with a clean bill of health, meaning that key striker Junior Moraes, who has 14 goals in all competitions this term, will start the game up front.
Atalanta, meanwhile, will hope that Luis Muriel, who joined over the summer, can score his 10th goal of the campaign in Ukraine on Wednesday.
The visitors are set to be without Josip Ilicic, whose muscle injury looks set to keep him sidelined until 2020.
However, Duvan Zapata has a chance of making a return for this game after resuming training earlier this month following a thigh injury sustained in October.
Shakhtar Donetsk possible starting lineup:
Pyatov; Dodo, Kryvtsov, Matviyenko, Ismaily; Stepanenko, Kovalenko, Alan Patrick, Tete, Konoplyanka; Moraes
Atalanta possible starting lineup:
Gollini; Toloi, Kjaer, Palomino; De Roon, Freuler, Hateboer, Gosens; Gomez, Pasalic, Muriel
We say: Shakhtar Donetsk 2-1 Atalanta
Atalanta's away record in this competition makes them underdogs in this game against Shakhtar, who will feel confident about reaching the knockout phase for the second time in as many seasons.
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