Last Italian champions in 1964, Bologna played in the old European Cup that same year but were knocked out of the competition in the preliminary round on a coin toss by Anderlecht.
That is why this season's campaign in the revamped Champions League feels much more like a debut than a return, and why some 40,000 fans celebrated in the centre of Bologna once qualification was secured last term.
Bologna finished fifth, their highest league placing since 1971, and took advantage of Serie A getting an extra spot in the elite club competition to try their luck against the continent's best teams.
Without last season's star players Joshua Zirkzee and Riccardo Calafiori, who both departed for the Premier League, and now-Juventus coach Thiago Motta, Bologna were undoubtedly weakened over the summer.
Motta's replacement Vincenzo Italiano has earned just one win from his new team's first six matches in all competitions, with Saturday's 1-1 drew with Atalanta their fifth stalemate this term.
"Atalanta are a Champions League-level team and the rhythm of play at Anfield on Wednesday will be the same," said Italiano after Saturday's draw.
Bologna are on one point in the tournament's new league phase following another draw, this one goalless, with Shakhtar Donetsk at a sodden Stadio Dell'Ara a fortnight ago.
But on their side is transfer maestro Giovanni Sartori, a maestro of signing young talent and pushing unfancied clubs further than they might ever have imagined.
Sartori was the man who built Chievo and Atalanta teams that reached the Champions League, with the latter now on another level thanks in part to his ability to build teams for clubs with limited financial means.
Another of those young signings, Argentine striker Santiago Castro, quickly settled in after arriving from Velez Sarsfield in January, and has started this season in fine form.
The 20-year-old has scored three times this season, with two of those goals cracking long-range strikes against Monza and Atalanta.
Castro has managed to keep summer signing Thijs Dallinga, who scored in both of Toulouse's group matches with Liverpool in last season's Europa League, out of the team.
He should be fit to play at Anfield as he trained with his teammates on Monday and looks to have shaken off a calf injury suffered against Atalanta.
"He's extraordinary. he's a young lad who's developing day by day, scored a great goal today and worked so hard," said Italiano.
"He's come here and got straight down to it... I hope his doesn't stop with his development because he's got a great future ahead of him."
It would take a huge performance and a serious off-night for Liverpool for Bologna to get anything from Anfield, let alone become the third Italian club to win there after Genoa in 1992 and Atalanta last season.
But for a team like Bologna, whose last major trophy was the 1974 Italian Cup, playing in matches of this magnitude is an honour in itself.
