Czech tactician Zdenek Zeman is a veteran of four Rome derbies, thanks to his previous two-year stint in charge of Roma, but he only managed to secure one victory before leaving the club in 1999.
Meanwhile, Bosnia's Vladimir Petkovic takes charge of a capital side for the first time in his career, having only moved to Italy this summer before guiding the Biancocelesti to fifth place after 11 games.
Opinions are divided on Zeman, with his unrelenting attacking philosophy earning him as many detractors as admirers over his 30-year career in management.
One fan is former Roma winger Bruno Conti, who told the Corriere dello Sport: "I absolutely love 'The Bohemian'.
"I had the good fortune to bump into him at the opera and I can assure you that he has been working like crazy this week.
"He knows how to approach important games, that's how he operates. And he will certainly have prepared well for this game.
"Petkovic has also proved to be an intelligent coach, he's made a big impression on the squad in a short amount of time and there's more to come."
Outspoken Lazio president Claudio Lotito damned the Giallorossi boss with faint praise, though, before backing his own tactician.
"Zeman is someone who always wants to be different," he said. "Why did I choose Petkovic? He struck me with his work ethic and he is a man of high moral fibre.
"He is highly ambitious and all these characteristics convinced me of his potential."
"Can we win a trophy this year? My philosophy has been to keep my dreams a secret, while looking to build up the club and achieve good results through hard work.
"In the last few years we have achieved a lot and I hope we get what we deserve."
Influential Roma players Pablo Osvaldo and Daniele De Rossi are unlikely to feature in the derby, while Lazio striker Miroslav Klose returns from suspension to boost the 'home' team.
Reigning champions Juventus look to get back on track at Pescara after Inter Milan ended their 49-game unbeaten run, with Cagliari hosting Catania in a fully-opened Stadio Is Arenas on Saturday night.
AC Milan would dearly like to be in Fiorentina's position of fourth and Massimiliano Allegri's Rossoneri will hope to build on a 5-1 victory over Chievo last time out.
The Flying Donkeys hope to bounce back from that hammering against Udinese, while Parma host basement boys Siena and Torino look to edge towards the top half of the table at the expense of lowly Bologna.
Also in the lower reaches are Genoa, with Luigi Del Neri plotting his first win in charge when Napoli visit the Stadio Luigi Ferraris.
The current momentum is with Inter Milan, who could capitalise on any slip up from Juve on Saturday night to go top with victory at Atalanta, with out-of-form sides Palermo and Sampdoria facing off in Sunday's early game.