The City manager believes it is a chance to change the club's history and establish a winning dynasty at the Etihad Stadium.
Victory would put City level on points with United, but with a superior goal difference, with two games to go as they aim to win the league for the first time since 1968.
And Mancini says that it is as significant to him as the 1992 European Cup final, when he captained Sampdoria against Barcelona.
"It is important to win everywhere but if you win, you change the history at a club like Manchester City that didn't win [the league] for 44 years," the Italian said.
"Our target should be United, Real Madrid and Barcelona. City are now in a good way for the future. I don't know if [we can win the league] every year but it is possible. I think City will be a top club for many years.
There is a school of thought that Sir Alex Ferguson, after winning 12 league titles in battles with more distant rivals, is uncomfortable about taking on the city's other club, but Mancini said: "It is good to win a title against your neighbour. It is better."
Whereas Mancini has emphasised how difficult City's final two matches - away at Newcastle United, who are competing for a Uefa Champions League place, and at home to relegation-threatened Queens Park Rangers - are, contrasting them with United's "easy" games (at home to Swansea City and away to Sunderland), Ferguson believes his side need to leave the Etihad Stadium with a point to retain their title.
"If City win they would probably go on to win it from there," the United manager said.
"Even though they've got to go to Newcastle, I think they would have a great chance."
Mancini countered: "We can win nine points but I don't know if we can win the title."
The duo disagreed, too, over Ferguson's suggestion that City have displaced Liverpool as United's major rivals.
"Liverpool are like United," the City manager said. "Liverpool have a big history. It is impossible to take their place."
But, as he noted, it is a sign of City's progress that they have 31 more points than the Merseysiders.
The Italian received a midweek endorsement, with Sheikh Mansour bin Zayed, the club's owner, indicating Mancini will remain in charge whether or not City win the league, but chose to downplay those comments.
"I am not important," the 47 year old said. "Only [the chairman] Khaldoon [Al Mubarak] and the Sheikh are important. If they want to change all the people they can put other good people in."
While Ferguson acknowledged he has two or three selection dilemmas, there will be a focus on Mancini's choice in attack.
Mario Balotelli was at his destructive best in October's 6-1 win at Old Trafford, when he scored City's first two goals, and is available again after serving a three-match suspension.
In his absence, City have scored 12 goals but Mancini said: "We also played well with Mario. The problem with Mario is that he can get a red card in every moment, also in the tunnel, or the dressing room, or at home."
Balotelli is likely to be on the bench, however, with Carlos Tevez having scored four goals in his absence.
The Argentine helped United win back-to-back league titles in his two seasons at Old Trafford, prompting suggestions he is fated to deliver a title-deciding goal against his former employers.
"I think that Carlos is more destined to score a more important goal in the history of the club," said Mancini, without specifying when.
If the striker is in an awkward position when facing former friends, so was Mancini when invited into Ferguson's office after inflicting the heaviest defeat of the 70 year old's managerial career. His stunning 6-1 win went unmentioned.
"We talked about red wine," the City manager said. "We didn't talk about the game."
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