The Holy See is the jurisdiction of the Pope, covering not only Rome, but also the universal Catholic Church.
Michael Corleone became involved with Vatican politics in 1979 when he attempted to buy his way into the world of legitimate banking through the Church owned Immobiliare, but he was thwarted by the bureaucracy and crooked nature of men such as Licio Lucchesi, Archbishop Gilday and Frederick Keinszig. However, he encountered Cardinal Lamberto during his time in Rome, who would become Pope John Paul, head of the entire Holy See, though only for a short period before Lucchesi had him poisoned.