Despite being the firstborn, he did not take over the family fortune due to his frail health, which was already visible during his childhood. In this, he was replaced by his younger brother. Meanwhile, Niccolò began a career in the Church. And since he was a man of unquestionable honesty and deep faith, at the final stage of the Council of Trent (1561-1563) he established a close bond with Cardinal Charles Borromeo – a declared supporter of reforms within the Church in the new spirit, which was to arouse the religiousness of the elites and the common people, but also of representatives of the Church, which, however, met with resistance of most of the clergy opposed to rigorous discipline. Another significant figure in the life of the future pope was the active in the city on the Tiber, charismatic Philip Neri (the creator of the Order of the Oratorians) – a restorer of religious life in the spirit of the Counterreformation. Sfondrati established closer ties with him after the year 1583 when he came to Rome in order to take over the responsibilities of the titular cardinal of the Church of Santa Cecilia.

After the death of Pope Urban VII, the cardinals gathered at the conclave deliberated for a long time. Spain controlled twenty-two from among the fifty-two cardinals assembled. The Spanish diplomacy presented a list of seven cardinals, who according to the King of Spain, Philip II could sit upon St. Peter's throne. This list also included the name of our protagonist, although he was ranked quite low. The Sfondrati family owed a great deal to Philip II – the title of Duke of the Holy Roman Empire, but also lands and posts in Lombardy. It was widely known, that Niccolò, was a man of gentle character, honest and pious – but also bereft of leadership and political ambitions. Ultimately it was he – the least controversial candidate – who received (after two months of deliberations)

– a favorable vote of the majority and to pay homage to his successor (Gregory XIII), who bestowed him with the cardinalship, took the name of Gregory XIV.

As was to be expected, as pope he supported the anti-French policy of Philip II, lashing out against the Huguenots, while also refusing Henry IV the right to the throne. In internal politics, he had to struggle with three enormous problems – an epidemic of the plague, banditry spreading in the State of the Church, and hunger. All of these inhibited the grand architectural and artistic projects of Gregory XIV, including the construction of his own posthumous chapel in the Basilica of Santa Maria Maggiore.

The sickly pope had neither the patience nor the experience to manage the affairs of the State of the Church. The person who did, and willingly occupied himself with it was his ambitious thirty-year-old nephew – Cardinal Paolo Camillo Sfondrati, who as was customary for nepots, concentrated in his hands all the power desiring to as quickly and effectively as possible take advantage of the time of the pontificate of his uncle for the good of the family. As was stated in a letter to Philip II, written by count-duke Olivares, the principal playmaker of the Spanish court in Rome, “the worst [is that] the (pope) gave all the authority over to his nephew, much greater authority than he is worthy of having”. However, the pope’s devotion to his nephew was unconditional and grew along with the worsening health of the pontiff. The lofty behavior of the cardinal nepot, his greediness, in stripping bare the papal treasury, but also “the human resource policies” cast a shadow upon the entire pontificate of Gregory XIV, and brought heavy criticism down upon him. The pope, on the other hand, listened to confessions and held mass on a daily basis.

He was buried in the Vatican Basilica at the column in the right nave, in a modest tomb made of light marble, which was only inscribed with the text GREGORIVS XIIII PONT MAX. The nephew did not fund a better tombstone for his uncle (as was the habit of nepots), occupied with bringing to fruition his own ambitions and costly projects.