After cruising through to the Europa League's last 16, Lazio visit Viktoria Plzen in Thursday's first leg at Stadion mesta Plzne.
Meeting for the first time, the Italian side and their Czech counterparts will fight it out to face either Bodo/Glimt or Olympiacos in the quarter-finals.
Match preview
Beating teams such as Ajax, Porto and Real Sociedad along the way, Lazio finished top of the inaugural league-phase table with a tally of 19 points, booking direct entry to the competition's last 16.
Having won six of their first seven games before losing a dead rubber to Braga, the Rome club are on track to surpass their best-ever continental campaign - eight wins during the 1999-2000 Champions League.
Ultimately aiming to win a first European trophy since the 1999 UEFA Super Cup, which followed hot on the heels of Cup Winners' Cup glory a few months earlier, they are considered to be one of this year's favourites.
However, the Biancocelesti have won only two of their last 13 knockout matches in Europe - losing on nine occasions - and they must still negotiate three rounds before the final takes place in Bilbao.
Also eliminated from the Coppa Italia last week, tamely losing 2-0 to Serie A leaders Inter Milan, they may have some psychological hurdles to get over.
Nonetheless, Marco Baroni's men will certainly be pepped up for the task by events on Sunday, when Pedro's 98th-minute penalty sent faltering top-four rivals AC Milan to a 2-1 defeat at San Siro.
While Milan now have a mountain to climb, Lazio are still locked in a battle with Bologna, Juventus, Fiorentina and perhaps even arch-rivals Roma to claim Champions League qualification.
Either side of hosting Udinese this weekend, Baroni's boys must take on Viktoria Plzen twice: with three wins from their last four European away games - as many as in the previous 25 - they might expect to take a lead into next week's second leg.
After reaching the Conference League quarter-finals last season, Plzen have taken the scenic route to the last 16 of UEFA's second-tier tournament one year later.
Miroslav Koubek's side finished outside of the top eight after losing two of their last three league-phase fixtures, but they subsequently came through the knockout playoffs.
Overturning a 1-0 first-leg deficit, star man Pavel Sulc was on target in a 3-0 second-leg win over Ferencvaros, setting up a high-profile tie that will conclude at Rome's Stadio Olimpico.
First, Viktoria welcome Lazio to Pilsen, having lost just one of 12 previous home matches in the Europa League and won no fewer than 10.
Sitting second in the Czech top flight, they have also won three of their last four on the domestic front, including a 4-1 cup win over Zlin.
However, history is not exactly on their side: Plzen have prevailed in just one of their last eight contests against Italian opposition - a home win over Lazio's city rivals Roma in the 2018 Champions League.
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Team News
Marco Baroni is still missing injured top scorer Taty Castellanos due to injury, so either Loum Tchaouna or Tijjani Noslin should lead Lazio's attack.
Mattia Zaccagni, Fisayo Dele-Bashiru and Elseid Hysaj are also unavailable, but Baroni expects full-back Adam Marusic to overcome a bruised knee.
Europa League specialist Pedro will hope his late goal against Milan results in promotion to the starting XI, and cup goalkeeper Christos Mandas is set to replace Ivan Provedel between the posts.
Meanwhile, Martin Jedlicka of Viktoria Plzen has been busy to this point of the competition, making the third-most saves.
Centre-back Sampson Dweh has made the most ball recoveries of any player in this season's Europa League, but he is now one of three Plzen defenders one booking away from suspension.
Featuring up front, Pavel Sulc and veteran striker Matej Vydra both have three goals and three assists to their name so far.
Viktoria Plzen possible starting lineup:
Jedlicka; Dweh, Markovic, Jemelka; Havel, Cerv, Kalvach, Cadu; Sulc; Vydra, Durosimni
Lazio possible starting lineup:
Mandas; Lazzari, Gila, Patric, Pellegrini; Guendouzi, Belahyane; Isaksen, Dia, Pedro; Noslin
We say: Viktoria Plzen 1-1 Lazio
Boasting a formidable home record in Europe, there is no doubt that Plzen can go toe-to-toe with league-phase top dogs Lazio.
Both sides should score at least once in an entertaining encounter, with the visitors heading back to Italy all square.
For data analysis of the most likely results, scorelines and more for this match please click here.
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