Liguria's capital city will come to a standstill on Wednesday night, as the third Derby della Madonnina of this season's trilogy sees mid-table rivals Genoa clash with old foes Sampdoria at the Marassi.
Both bosses effectively forfeited any hope of points against top-four contenders at the weekend, resting a whole swathe of first-teamers in advance of the 103rd staging of an all-consuming Calcio rivalry.
The oldest derby in Italian football, with the first match being played in 1902 when Sampdoria were still known as Andrea Doria, this special occasion's name is derived from the Torre della Lanterna, the ancient landmark and main lighthouse for the city's port.
Nominally the home side on this occasion, Genoa may be slightly behind in the current Serie A standings, but are effectively ahead against Samp this term, after a 1-1 league draw in the autumn was swiftly followed by Coppa Italia fourth round success for the Grifone.
Previously unbeaten in seven league games, Genoa had bettered the points tallies of every club but Inter, Lazio and Juventus since mid-January ahead of the weekend's fixtures, raising eyebrows - plus their long-suffering fans' hopes - with a rapid reversal in form.
When previously they looked an abject proposition, destined to dice with demotion, head coach Davide Ballardini returned to the dugout for a fourth time earlier this term and has had a transformational effect. Since the former Palermo boss re-joined the club, they have lost just two league games from eleven - the second of which came at San Siro, against league leaders Inter last Sunday.
Rampant Romelu Lukaku took less than a minute to stride clear of the Genoa defence in the second city, netting the opening goal in a comprehensive 3-0 victory for the Nerazzurri. Clearly, the several squad players who were offered a chance to stake their claim for more regular football were unable to rise to the challenge against one of Europe's most in-form teams, as Inter fired in 24 shots on goal to Genoa's three.
Ballardini stated afterwards that he had taken fitness levels, players at risk of suspension due to accumulation of yellow cards and those who struggle to complete three games per week into account when selecting his XI. Undoubtedly, though, his decisions were made with an eye on the all-important Derby.
Notwithstanding that potentially momentum-halting reverse, the Grifone still have intact their six-match home unbeaten streak, dating back to November - when they lost to lowly Parma - but, of course, their opponents this time will also effectively enjoy 'home' advantage too.
Though enjoying the stability of tenth place in the Serie A standings and with a four-point buffer over their co-tenants at the iconic Stadio Luigi Ferraris, having previously enjoyed a previous run of three wins from four, Sampdoria have since won only one of their last five Serie A outings.
Perhaps unfairly dubbed 'The Tinkerman' during his time in charge of a large squad at Chelsea, coach Claudio Ranieri certainly rotated a little too much over the weekend, in a 2-0 home defeat to Atalanta, when the rarely-used duo of Antonino La Gumina and Valerio Verre were paired up front. It was telling that when both were replaced by first-teamers Keita Balde and Fabio Quagliarella late on, the Atalanta coaching staff audibly roared at their defence to prepare for some "real strikers".
Even at this advanced stage of a career filled with great goals and wonderful memories at a series of clubs, Quagliarella has been the leading attacking threat for Sampdoria again this season, scoring on eight occasions despite not always starting - particularly when there is more than one game in a week.
On Wednesday, the former Azzurri star will go head-to-head with Genoa's in-form Mattia Destro - one of the top flight's most prolific strikers since December - as the former international colleagues carry the hopes of each side of the divided city on their shoulders.
Though neither man scored in the previous top-flight iteration of the derby, which saw Jakub Jankto's first-half goal for Samp rapidly cancelled out by Gianluca Scamacca equalising for Genoa just five minutes later, few would bet against both men being instrumental in deciding the final chapter of the 2020-21 triptych.
Notoriously unpredictable this season, it would be risky to rule out Ranieri's men this time, as the well-travelled tactician is always a man for the big occasion - already labelling it "the match of the year" - but their city rivals have been resurgent of late and cannot be discounted either.
Genoa Serie A form: WWWDDL
Sampdoria Serie A form: WLDWLL
Following wholesale changes up front at the weekend, Claudio Ranieri will reinstate top scorer Fabio Quagliarella and his most regular partner in recent weeks, Keita Balde, to the starting XI. Veteran winger Antonio Candreva comes back in on the right, while young Mikkel Damsgaard may miss out or perhaps play in place of Jakub Jankto on the left.
Sampdoria will be without back-up forward Ernesto Torregrossa, who is nursing a calf injury, but otherwise have a clean bill of health since Manolo Gabbiadini's return to fitness. With Adrien Silva returning from suspension, after missing the defeat to Atalanta, he must contest a three-way battle for two places in the engine room - alongside incumbents Albin Ekdal and Morten Thorsby.
Even though Davide Ballardini will be unable to call upon full-back Luca Pellegrini (shoulder), midfielder Francesco Cassata and defender Davide Biraschi (thigh) due to injury, his key men are fit and mostly well rested after some major rotation of resources in Milan last weekend.
Leading goalscorer Mattia Destro will replace Marko Pjaca in attack, while Miha Zajc and Milan Badelj are set to return to the midfield three in Genoa's now customary 3-5-2. Eldor Shomurodov and Goran Pandev are in direct competition for a place, as Gianluca Scamacca is expected to drop to the bench.
Genoa possible starting lineup:
Perin; Masiello, Radovanovic, Criscito; Zappacosta, Strootman, Badelj, Zajc, Czyborra; Shomurodov, Destro
Sampdoria possible starting lineup:
Audero; Bereszynski, Yoshida, Colley, Augello; Candreva, Silva, Ekdal, Jankto; Keita, Quagliarella
We say: Genoa 2-1 Sampdoria
A close one to call, as in many derbies - which often narrow the gap between sides and reduce the outcome down to decisive moments - but Genoa can complete a second win of the season over their old foes on Wednesday.
Providing their new-found sense of direction and cohesion has not been sacrificed at the altar of pre-match rotation by Ballardini, the Grifone certainly have it within them to close the once gaping chasm between the clubs in the Serie A standings down to a single point.