Second-placed Roma visit Napoli on Sunday buoyed by their Champions League win over Real Madrid and hoping the Neapolitans won't repeat their giant-killing feat of a week ago against Inter Milan.
A win should keep the Romans within shouting distance of Inter who have an apparently easier task at home to second-last Reggina on Saturday.
Inter lost their first match of the season at the San Paolo last week, bringing Roma, who enjoyed a thumping 4-0 win over Parma, to within six points again and reopening the books on the title race.
Roma will have due respect for the San Paolo cauldron but have been tempered by their Wednesday visit to the red-hot atmosphere of the Bernabeu where they pulled off a 2-1 win to move into the Champions quarter-finals for the second year running.
Coach Luciano Spalletti will again have a full roster to call on after defender Philippe Mexes served out a ban inflicted in Inter's last-gasp draw at the Olimpico two games ago.
Napoli are looking good again after early season wins against Inter and Juventus and a spectacular 4-4 draw at Roma in the corresponding fixture in October.
Inter, on the other hand, are still cramped by injury woes with centre backs Ivan Cordoba and Walter Samuel out for the rest of the season and left back Maxwell injured. Right-back and sometime central defender Christian Chivu is struggling to make Saturday's game (17:00 GMT) after bruising his shoulder at Napoli.
Medical staff are working frantically to get him fit but Chivu may have to wait for Tuesday's Champions League last 16 second leg against Liverpool, where Inter will be trying to rub out a 2-0 deficit from the first leg at Anfield.
Relatively untried Colombian Nelson Rivas will probably take Chivu's place against Reggina.
Coach Roberto Mancini will also be tempted to rest key players such as Sweden star Zlatan Ibrahimovic ahead of the make-or-break Liverpool tie.
Unlike their bitter cross-town rivals AC Milan, who have rattled up seven Champions League wins including five since 1989, Inter has been waiting since 1965 to add to their two European Cup successes.
Milan visit Empoli to resume the hunt for their remaining goal of the season, a fourth-place Champions League berth, after being dumped out of Europe by Arsenal at the San Siro Tuesday night.
The reigning European champions have again faltered in the league lately to drop four points behind fourth-placed Fiorentina with 12 matches left.
Empoli are in 16th slot, a point above the drop zone, but will be cheered by memories of their 1-0 win in Milan in September.
Third-placed Juventus, seven points behind Roma, visit 8th-placed Genoa in Sunday night's game (19:30 GMT) hoping to bounce back from last week's rare defeat at home to Fiorentina.
But they will again be without influential midfielder Pavel Nedved, who was sorely missed against the Florentines.
Fiorentina, now just a point below Juve, travel to 13th-placed Siena without injured striker Adrian Mutu in the Tuscan derby on Sunday.
Seventh-placed Sampdoria visit Parma - in sixteenth place but now out of the relegation zone after a couple of good results - without controversial striker Antonio Cassano.
The former Roma and Real Madrid striker has been banned for five games following one of the more spectacular of his characteristic 'cassanate' (temper tantrums) against the ref in Sunday's otherwise entertaining 2-2 draw with Torino last week.
