On June 11, 1251, the pope issued instructions from Genoa to Vincentius of Milan and Joannes of Vercelli, to undertake the office of inquisitor, jointly or severally, in Venice and other parts of Lombardy.

On the same day, and with the same form letter ("Misericors et Miserator"), the pope also appointed Peter of Verona and Vivianus of Bergamo to the same task in the area of Cremona and other cities of Lombardy.

The pope was also prepared to take on Frederick's sons Manfred and Enzo (Ezolino) of Sardinia, as he indicated in a letter to the Dominican Bishop of Treviso and the Prior of Mantua.

Alexander replied, urging them to act boldly and independently, against any manner or quality of person, but to continue to consult the Holy See in difficult cases.

[17] Known for his tireless energy and his commitment to simplicity, John made personal visits—typically on foot—to almost all the Dominican houses, urging his fellow friars to observe faithfully the Rule and Constitutions of the Order.

John of Vercelli and the members of the Order carried that plan to completion, providing a new shrine for Dominic's body in the apse of their church.

Already on March 15, 1267, Pope Clement IV provided a bull, granting a series of indulgences for those visiting the shrine during the week centered on Dominic's feast day.

[20] John is known to have consulted Thomas Aquinas officially on several occasions on matters pertaining to theology and the teaching of Pierre de Tarantaise.

[21] During his administration, Pope Gregory X entrusted the Dominican Order with the task of trying to establish peace among the warring States of the Italian peninsula.

Additionally, John was also given the task of preparing a framework for the Second Council of Lyons, held in 1274 in an attempt to unify the Eastern and Western Churches.

[26] Cardinal Ottobono Fieschi was elected on July 11, 1276, and took the name Adrian V. In August, even before his consecration and coronation, he travelled to Viterbo, partially to escape the Roman summer, but also because he wished to meet with the Emperor-elect Rudolf.

This was not surprising, since, after a General Chapter, and this one in Pisa, the leaders of the Order of Preachers would have business of all sorts to do with the Curia;[27] the decision to go to Rome was much happier, since one of their own had been elected pope.

Once order was restored, however, the Conclave began, and in one day, on September 8, produced a new pope, Cardinal Peter Julian of Lisbon, who chose to be called John XXI.

[30] The urgency of their mission was repeated in a letter from the College of Cardinals, written during the Sede Vacante[31] following the death of Pope John XXI on May 16, 1277.

[33] On March 12, 1278, Hieronymus Masci was named a cardinal,[34] but the legates had their orders reinforced by a letter from Nicholas III dated April 4, 1278.

John of Vercelli insisted on the rule instituted by Dominic himself that Friars of the Order should travel on foot, never using a horse or a wheeled vehicle.