Antonio Conte's Inter Milan take their title push to Napoli on Sunday looking to extend their winning streak as Juventus travel to Champions League rivals Atalanta.
Inter are 11 points ahead of second-placed AC Milan and chasing a 12th consecutive league win to push them closer to a first title since 2010.
Champions Juventus are third, a further point back, with their nine-year reign looking set to end.
"We never expected to be this far ahead with eight games to go," said Inter defender Milan Skriniar.
"Every day Conte tells us that we must work without looking at the advantage and above all not to make calculations."
Stefano Pioli's second-placed Milan take on 13th-placed Genoa looking to end their home drought.
The northerners have not won in the San Siro in over two months and will be without suspended forward Zlatan Ibrahimovic.
A slip-up could allow either Juventus or Atalanta to move second with both teams going head-to-head in Bergamo.
Conte has won his last three league games against fifth-placed Napoli, who are two points off the Champions League berths.
"We're working really hard, hungry to reach our goal," said Inter forward Romelu Lukaku who helped the team finish runners-up last season.
"Last year there were many ups and downs, but if we look at the team there are many young players and I think we have all taken a next step."
Gennaro Gattuso's Napoli will be without suspended Hirving Lozano with Alex Meret in goal for injured David Ospina.
Napoli have won at least 19 of their opening 30 Serie A games for just the fifth time.
The previous times they finished the season in the top three of the table.
In the Champions League race nine points separate second-placed Milan and Roma in seventh.
In Bergamo, Atalanta and Juventus clash in a dress rehearsal for next month's Italian Cup final.
Third-placed Juventus are just one point ahead of Atalanta, who occupy the final elite-European berth.
With eight games left, both sides need to win.
Atalanta travel next weekend to European rivals Roma, with their final game this season against AC Milan.
Juventus come up against both Milan teams in their run to the end of the season.
Atalanta haven't beaten Juventus in Serie A in 20 years going back to February 2001.
But in all competitions Juve have have won just one of their last six meetings in November 2019.
Juve striker Cristiano Ronaldo drew a blank last time out to his frustation as the 36-year-old targets the top Serie A scorer prize this season which he currently leads with 25 goals.
Lazio, in sixth, host Benevento with city rivals Roma, a point behind, travelling to 17th-placed Torino, riding high after advancing to the Europa League semi-finals.
Cagliari host relegation-rivals Parma, in a match which could prove decisive for top-flight football next season.
One to watch: Duvan Zapata
Atalanta's Duvan Zapata has scored four goals in his last three Serie A games to bring his tally to 13 this season.
Despite a brace last time against Fiorentina the 30-year-old Colombian was furious at his "missed chances". Against Juventus he has impressive record with seven goals in eight games in all competitions.
71 - Atalanta's goals, the top attack in Serie A
12 - Champions Juve's points off top spot
11 - Inter's winning streak
5 - Cagliari's points off top flight survival
Fixtures (times GMT)
Crotone v Udinese, Sampdoria v Hellas Verona (both 1300), Sassuolo v Fiorentina (1600), Cagliari v Parma (1845)
AC Milan v Genoa (1030), Atalanta v Juventus, Bologna v Spezia, Lazio v Benevento (all 1300), Torino v AS Roma (1600), Napoli v Inter Milan (1845)