Piazza Scossacavalli was the center of the so–called spina (the name derives from its resemblance with the median strip of a Roman circus), composed of several blocks elongated in E–W direction between the castle and Saint Peter.

[24] Adriano Castellesi, treasurer of Pope Alexander VI and later Cardinal of Corneto (today's Tarquinia), in 1504 bought the plots at the north side of the piazza, occupied by a vegetable garden and several small houses,[17] and let erect there (possibly by Donato Bramante) a palace, which follows the outlines of the Palazzo della Cancelleria.

[26] Along the western side of piazza Scossacavalli, at the corner with Borgo Vecchio, in the 15th century lay a house property of Bartolomeo Zon [27] which hosted two deposed queens: Catherine of Bosnia, which lived there in 1477–78,[28] and Charlotte of Cyprus.

[30] On the east side, shortly after 1520 the confraternity of the Blessed Sacrament started to reconstruct the church of San Giacomo, choosing as architect Antonio da Sangallo the Younger, but due to lack of funds its facade was still unfinished in 1590;[31] anyway, thanks to a legacy two years later the construction was finished.

[31] The church was separated from Borgo Nuovo by a small lane and a house belonging to the near Hospital of Santo Spirito; during the reign of Sixtus IV it had been rented for a long time by a valiant condottiero, Andrea della Casa Dennesia.

[32] At the center of the square in 1614 was erected by Carlo Maderno (or Giovanni Vasanzio) a fountain with a mixtilinear basin surmounted by a cup bearing the ensigns of Pope Paul V Borghese (r. 1605–21) (the eagle and the drake).

[33] In the 19th century, the only major intervention in Piazza Scossacavalli was the construction inside Palazzo dei Convertendi of a richly decorated oratory dedicated to San Filippo Neri with an entrance on the square.

[35] Among the buildings which bordered the square, the Church of San Giacomo was demolished in 1937;[36] the Palazzo dei Penitenzieri, which was in a dilapidated state,[37] was left in place but underwent a heavy restoration in 1949 and now faces the south side of Via della Conciliazione; the Palazzo dei Convertendi was demolished but some elements of its prospect along Borgo Nuovo, included the portal surmounted by a beautiful balcony attributed to Carlo Fontana or Baldassarre Peruzzi,[38] were reused in a modern palace bearing the same name and erected along the north side of Via della Conciliazione; Palazzo Torlonia remained untouched, being the only building not to be altered during the works for the opening of the new road,[39] This building, which now belongs to the Torlonia family,[25] and is now part of the north side of Via della Conciliazione.