The museum comes from an idea of the professor Adelfio Elio Cardinale, Director of the Institute of Radiology of the University of Palermo (from 1992 to 2001), in occasion of the analysis of some problematics connected to the renewal of the equipments of the Institute of Radiology and the approach of the 100th anniversary of the discovery of X-ray by Wilhelm Conrad Rӧntgen (8 November 1895 – 8 November 1995). An occasion of great importance to celebrate the birth of a museum dedicated to the History of Radiology.
On the basis of these contingencies, it began an intense research of instruments, equipments, books and documents of various type and from various sources (public and private) about Radiology.
Inaugurated in December 1995 by the mayor of Palermo, professor Leoluca Orlando, with the president of the Italian Society of Radiology in that period, professor Ludovico Dalla Palma, and with the director of the Rӧntgen Museum di Ramscheild, Dr. Uhlrich Henning, during the celebration of the 100th anniversary of the X-ray discovery.
The Museum is the only one of its kind in Italy and together with the Musèe di Parigi, il Rӧntgen Museum di Ramscheid and il Museum Belga of Radiology of Bruxelles, is one of the four present in Europe.

At the end of the 90ies, the Institute of Radiology, entitled to Pietro Cignolini, was incorporated to the Section of Radiological Sciences of the Department of Biopathology and Medical and Forensic Biotechnologies of the School of Medicine of the University of Palermo.

In 2012, the Museum of Radiology was reorganised and divided in six sections or thematic itineraries located in the rooms of the first floor and called "history of Radiology", "evolution of the devices", "collection of X-ray tube and valve", "X-ray facility of the 30ies", "Cignolini's room", "educational path".

The reorganization of the scientific collection of the Museum was accompanied by a new museum display, and in the 2013 by also a graphical restyling of the illustrative captions of the exhibited devices and equipments. Moreover it was realized the creation of new educational panels and the official logo of the Museum.

The scientific collection of the Museum is composed, besides the devices, the equipments and the objects related to radiology, radiotherapy, electrotherapy, Marconi-therapy, ultrasoundtherapy and also to surgical instrument, instrument of Physics and photographic equipments.

In 2014 it was made a campaign of cataloging of all scientific equipment and instruments, that allowed the precise identification and dating of every exhibit and the quantification of the objects in about 327 elements.
Lastly, in the October 2018 the Museum had a new inauguration after the enlargement of the collection and a new museum and graphical layout.