The so-called Columbus' House is located not far from the gate of Porta Soprana, just outside the medieval walls. It is probably an 18th century reconstruction of the original medieval building, where the discoverer of the Americas spent his youth. The house was likely destroyed during the bombing by the French fleet of King Louis XIV that hit Genoa in 1684. The building has two floors: the ground floor was used as a workshop by his father, Domenico Columbus, who dealt in wool weaving and trade; the home of the family was upstairs. According to written sources, the navigator must have lived here between 1455 and 1470.

In addition to the damage caused by the French bombing of 1684, the building was also affected by the intense building development in the area of Ponticello, where it was located. The district took its name from the small street called Vico Dritto Ponticello, which no longer exists, located just outside the ancient Porta Soprana on St. Andrew Cloister, where the house stands. According to Genoese historian Marcello Staglieno, who is credited with the discovery of the home of Columbus, at the time of the navigator the building had two or perhaps three floors and was restored on the basis of the original remains. The archival documents found by Genoese historians suggest that Domenico Columbus, father of the great navigator, moved with his family in the Vico Dritto Ponticello in 1455 when Columbus was only four years old. The ground floor of the house was used as a workshop; the front door was on the left of the façade. A wooden truss ceiling separates it from the upper floor, probably as in the original structure.
In 1887, the house was purchased by the Municipality of Genoa, as concrete evidence of the provenance of the Genoese navigator. The building was thus included in the restoration program of the Porta Soprana, which allowed for its survival despite the transformations of the centre between the late 19th century and the 1930s. A plaque on the main front of the house reads: “No home is more worthy of consideration that this one, where Christopher Columbus spent between paternal walls his early youth”.