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In 1210, when an adjacent cemetery ran out of space, a room was built to hold bones. A church was attached in 1269. Renovated in 1679, it was destroyed by a fire in 1712. A new bigger church was then attached to the older one and dedicated to Saint Bernardino of Siena.
The church’s origins date to 1145, when a hospital and a cemetery were built in front of the basilica of Santo Stefano Maggiore. In 1210 a chamber was built to house bones from the cemetery, next to which a church was built in 1269. It was restored for the first time in 1679 by Giovanni Andrea Biffi, who modified the façade and decorated the walls of the ossuary with human skulls and tibiae.
The church was destroyed in 1712; it was replaced by a new edifice designed by Carlo Giuseppe Merlo, featuring a central plan and larger size reflecting the increasing popularity of the ossuary. The new church, connected to the former one by an ambulatory, was entitled to St. Bernardino of Siena.
The façade was completed in 1776.