After winning a fifth straight away game in the league without conceding a single goal, the Scudetto favourites return to Stadio Maradona, where their visitors will target victory to stay in good shape for a top-four finish.
Match preview
Having secured a seventh straight league victory at Sassuolo before taking a 2-0 lead in their Champions League tie with Eintracht Frankfurt, Napoli added a third success in the space of a week when they saw off Empoli last time out.
Stretching further clear of closest rival Lautaro Martinez in the race to be crowned this year's Capocannoniere, Victor Osimhen scored for an eighth successive Serie A match - the first man to reach that tally since Cristiano Ronaldo more than three years ago.
The Partenopei ultimately secured a 2-0 result at Stadio Castellani, despite Mario Rui being sent off midway through the second half, when the VAR intervened after he lashed out at Empoli's Francesco Caputo.
Surely bound for a long-desired title triumph in the coming months - or perhaps even weeks - Napoli have now won 21 of their 24 league fixtures, scoring 58 goals and conceding just 15.
Following Inter's loss at Bologna last weekend, Luciano Spalletti's men can stretch their lead to scarcely credible proportions when Lazio come to town, and even other Serie A coaches have openly declared his side 'champions-elect' in recent days.
Kicking off the league's 25th round on Friday night, they will be attempting to complete the double over their Roman rivals, after a 2-1 win at Stadio Olimpico in September's reverse fixture, since when the gap between the two clubs has grown ever wider.
While Lazio have kept things tight on the road this season - letting in just seven league goals away from home: a record matched only by Napoli - their latest opponents are not only unbeaten on home soil in Serie A but also average almost three goals per game at Stadio Maradona.
The size of the task awaiting Maurizio Sarri as he prepares to visit his former club is quite clear, then, but his current team remain very much on course for Champions League football next term.
After Luis Alberto's 80th-minute strike at home to Sampdoria added another three points to their total on Monday, the Biancocelesti closed to within two points of the Milan clubs in second and third.
Arch-rivals Roma are another of the contenders pursuing just three cherished spots behind Napoli, and Lazio will also aim to emulate the Giallorossi's achievement of winning the Europa Conference League, having edged out CFR Cluj in that competition's playoffs last week.
Sarri's side are behind only Juventus for clean sheets kept in Serie A this season, partly compensating for Ciro Immobile's lack of form and fitness up front, and they may believe if any team can hold the leaders for 90 minutes it would be them. Of course, Juve thought similar before being humbled 5-1 in Naples just after the winter break.
In addition to their loss when the teams most recently met, Lazio were beaten both home and away by Napoli last term, so will be particularly eager to end that streak against all the odds.
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Lazio Serie A form:
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Team News
Following his dismissal on Saturday, Napoli's Mario Rui must now serve a two-match suspension and should be replaced by Mathias Olivera at left-back.
Only Giacomo Raspadori is unavailable due to injury, but Luciano Spalletti may move to freshen up his starting XI after a busy period at home and abroad by bringing Eljif Elmas into midfield; Matteo Politano could also replace Hirving Lozano on the right flank.
Although Giovanni Simeone would delight in leading the line against his father's former club, instead Victor Osimhen will seek a ninth straight goalscoring appearance in Serie A.
Meanwhile, Lazio have also been busy in Europe and had to rush back Sergej Milinkovic-Savic and Mattia Zaccagni from illness to play a part on Monday.
Both should be fit to play in Naples, while Pedro continues to wear a protective mask to shield his broken nose and - despite also sustaining a hand injury - will battle it out with Zaccagni for selection.
Maurizio Sarri must keep his fingers crossed that Alessio Romagnoli will be cleared to return at centre-back for the visitors, as Nicolo Casale is suspended due to accumulated bookings.
Napoli possible starting lineup:
Meret; Di Lorenzo, Kim, Rrahmani, Olivera; Anguissa, Lobotka, Elmas; Politano, Osimhen, Kvaratskhelia
Lazio possible starting lineup:
Provedel; Marusic, Romagnoli, Patric, Hysaj; Milinkovic-Savic, Cataldi, Alberto; Anderson, Immobile, Zaccagni