Following a victory in midweek, AC Milan return to Stadio Alberto Picco for the first time since Spezia's historic triumph over them in Liguria last February.
One of the first faltering steps as they faded out of Scudetto contention, the Rossoneri will want to avenge that result and keep the pressure on their rivals at the top of this term's Serie A standings.
Match preview
With a win over Venezia on Wednesday evening, Milan equalled the 13 points they collected after five games last season - having only matched or surpassed that tally twice since the turn of the century - and put themselves within touching distance of flawless Napoli at the summit of Serie A.
After resting a few first-teamers for the visit of their newly-promoted opponents, Stefano Pioli's side were ultimately indebted to flying full-back Theo Hernandez, who made a major impact from the bench to help the Rossoneri claim a 2-0 victory with a well-struck goal and an assist.
That maintained their unbeaten start to the league campaign - though they did fall to defeat at Anfield upon their long-awaited return to the Champions League - as the second city giants aim to mount another challenge for their first Scudetto since 2011.
However, Pioli and company now travel to La Spezia with the shadow of an infamous loss looming over them, after they were beaten 2-0 by the home side when they visited the Picco for the first time in Serie A history last term.
Such setbacks must be avoided at all costs this season, if the Rossoneri are to sustain their push for the top step of the podium; particularly as city rivals Inter look undisturbed by their summertime departures, while Napoli and Roma seem to have improved again too.
Ahead of a week when they host Spanish champions Atletico Madrid in Europe before an all-Lombardy clash with Atalanta, only three points will do for the exacting Pioli on Saturday afternoon, but they are unlikely to come easily.
Just days after they claimed their first league win of the season in dramatic fashion, when recent acquisition Mehdi Bourabia stole the points in the 94th minute versus Venezia, it briefly appeared that Spezia were on course to surpass last season's achievement in humbling Milan.
Leading 2-1 against serial champions Juventus with over an hour played, the Aquilotti faithful were starting to dream of writing a new page in the Ligurian club's history, but events in the final 25 minutes ultimately left them empty-handed.
After Janis Antiste cut inside with ease to confidently beat Wojciech Szczesny at his near post, Juve were reeling, but the Old Lady regained composure and ran out 3-2 winners thanks to Federico Chiesa and Matthijs de Ligt finding the Spezia net in quick succession.
Nonetheless, spirits will have been raised inside the squad managed by former Inter midfielder Thiago Motta, as they prepare to host another giant of Calcio at the weekend, before their fixture list eases with games against teams such as Verona, Salernitana and Genoa before the end of next month.
Spezia have now lost three of their last five home matches in Serie A, so will surely prioritise avoiding defeat on Saturday - with one of the division's worst defensive records also undermining their cause.
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Team News
Recently short of centre-forward options, Milan could have French striker Olivier Giroud back on the bench this weekend, after he returned to full training during the week.
The Rossoneri have been without both Giroud and Zlatan Ibrahimovic in recent games, with Ante Rebic leading the line in their absence, and the versatile Croatia international is favourite to retain that role in Stefano Pioli's XI.
The experienced coach may well return a few familiar faces to his lineup, following a raft of midweek changes, as Theo Hernandez, Fikayo Tomori and Franck Kessie are all expected to start.
Centre-back Simon Kjaer recently joined a lengthening injury list for the Rossoneri, with Ibrahimovic (Achilles), Rade Krunic (muscular), Tiemoue Bakayoko (leg) and Davide Calabria (muscular) all set to be excluded, though summer signing Junior Messias might be fit to feature at some stage.
Should club captain Calabria remain absent, Alessandro Florenzi and Pierre Kalulu will contend for a place at right-back.
Spezia, meanwhile, were without Martin Erlic, Kevin Agudelo, Ebrima Colley, Viktor Kovalenko, Polish wing-back Arkadiusz Reca and Leo Sena on Wednesday, and they are all poised to miss out again.
Petko Hristov should therefore continue in the centre of the back four, with on-loan Rey Manaj battling it out with midweek goalscorer Janis Antiste and last season's star man M'Bala Nzola to start up front. Eddie Salcedo is set for a second-half role from the bench.
Spezia possible starting lineup:
Zoet; Amian, Hristov, Nikolaou, Bastoni; Ferrer, Bourabia, Maggiore; Verde, Antiste, Gyasi
AC Milan possible starting lineup:
Maignan; Kalulu, Tomori, Romagnoli, Hernandez; Tonali, Kessie; Saelemaekers, Diaz, Leao; Rebic
We say: Spezia 1-3 AC Milan
Injuries and the distraction of tougher tests to come may well take the edge off Milan's efforts at the Picco, but their young and talented squad can secure a fifth win from six due to their hosts' defensive deficiencies.
Clearly, on their day, Spezia can pose a threat to any side, but Thiago Motta's approach leaves them open to being badly stung by counter-attacks - perfect for the Rossoneri's pacy wide men to ruthlessly expose.
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