The Cathedral of Manfredonia is dedicated to St. Lorenzo Maiorano, patron of the city. In it are preserved the relics of the saint and the icon of Our Lady of Siponto.

The cathedral was begun February 7, 1270 and ended in 1274. The cathedral was destroyed by the Turks in 1620, but resources in 1700 from the ruins of the ancient temple to Angevine about the ordinary diocesan Bishop Bartholomew of Cueva, Cardinal Vincenzo Maria Orsini and Monsignor Andrea Cesarano. Bartolomeo della Cueva he changed the entrance making it open from the other side, stared at the stalls for the canons and the altar was before the title page. Formerly the main entrance was located on the side of the bell tower built by Cardinal Orsini in 1677. The bell of the old bell-mail archbishop Marullo in 1646 and merged by the famous Neapolitan Onofrio Giordano was put to the new bell tower. In the cathedral there are frescoes of 1940-1941, the Penati Christmas from Milan, Julius III and Benedict XIII, apparition of St. Lawrence with Totila, the Saints Siponto Giustino, Barbato and the martyrs of Forconio. There are also preserved the paintings of the archbishops Orsini, Muscettola, Rivera, Cut it, in addition to some parchments, books of baptisms from 1600 to today, and other miscellaneous books. The protector of Manfredonia is the Madonna of Siponto, the patron saint Lorenzo Maiorano. The framework and the image of the Madonna with the splendid golden crown studded with diamonds were blessed by Cardinal Angelo Giuseppe Roncalli, the day August 28, 1955, day of the coronation. Fr. Matteo Orsini, a Dominican, moved 30 October 1327 from Siponto in Manfredonia the body of St. Lawrence Siponto in the cathedral.

 Manfredonia Cathedral and Orsini belltower, 30s
During the fire and the destruction of the cathedral by the Turks led by General Ali Pasha was destroyed around the San Lorenzo body, minus the right arm, the same who had so often blessed the crowds and remains today, hanging like a sprinkler on the foreheads of the faithful. Urn, placed under the main altar of our cathedral, preserves the sacred relic. In the sixties, at the behest of Bishop Cesarano it was built the new facade in travertine marble, in which was included the marble statue of John XXIII work of Siponto sculptor Aaron of the Old.