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Hidden in the shadow of modern buildings, just a few meters from St. Peter’s Basilica, the Church of San Lorenzo is one of the constructions that were ‘saved’ from destruction during the urban redevelopment of the period 1936–1950. During the construction of Via della Conciliazione – which today leads to the Vatican – some parts of the church, including the atrium and the façade, were nevertheless destroyed, so its presence is only noticeable to those walking along Borgo S. Spirito. At the end of this street, towards St. Peter’s, on the right, a small medieval apse, extensively restored, appears. To access it, one must enter through door number 24 of the adjacent Via Pfeiffer.

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The earliest mention of this church dates back to 1143, cited under the name Sanctus Laurentius in Portico Maiore, although its origins are even older, as it was built on top of a church dedicated to Saint Stephen or to Saint Galla, a widow from the 6th century, a noble Roman matron to whom, according to tradition, the Virgin Mary appeared. This ancient basilica, which housed a monastery of virgins, was most likely destroyed during barbarian invasions. Rebuilt in honor of Saint Lawrence, the martyr who distributed the Church’s wealth to the poor to prevent it from falling into pagan hands, it was called San Lorenzo in Piscibus due to its proximity to a fish market.

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In the 16th century, the church was entrusted to the Poor Clares, who, under Pope Leo X (1513–1521), were relocated to another site. The church then passed to a lay community from Santo Spirito in Sassia before being incorporated into a grand patrician palace owned by Cardinal Francesco Armellini, who initiated the first restoration works. Later, Cardinal Cesi oversaw the opening of windows and the embellishment of the main altar with a painting depicting The Wedding Ceremony of the Virgin.

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In 1659, the Brothers of the Christian Schools took possession of the church, which was in a pitiful state, as indicated by an inventory from that time. Extensive reconstruction works were undertaken under the direction of decorator Francesco Massan, a student of Borromini. In 1733, the Brothers of the Christian Schools purchased three houses adjacent to the church and received a significant sum of money. They then commissioned architect Domenico Navone to build a large atrium and a new façade.