Opened in 1914 using the collections of the Museo Civico dei Peloritani, it is situated in Viale della Libertà, in front of the tram north station. It occupies some buildings once belonging to the textile factory Melinghoff, in an area where there was the Archimandrite of SS. Salvatore dei Greci, a magnificent Brazilian monastery. After the earthquake of 1908, all the works of art of the ancient city were collected in this place, called Spianata dei Greci. Because of the big number of works and acquisitions given back to the city, the present buildings are insufficient to exhibit them all. For many years, the city is waiting for the opening of the new adjoining pavilions. At the moment the exhibition is limited to the medieval and modern sections. The building is preceded by a garden and a terrace in which it is possible to admire statues belonging to the destroyed buildings.  

Room I hosts the works of the Byzantine-Norman culture, among which is the niche mosaic from the destroyed S. Gregorio church called Madonna in trono con bambino e offerente, known as Ciambretta, made by an unknown Byzantine author, dated back to the 13th century, and the sarcophagus of the archimandrite Luca, who died in 1175.   

Room II shows works of the Gothic culture: a statue called Madonna seduta col Bambino, also known as Madonna degli Storpi, made around 1333 by Goro di Gregorio. 

Room III is dedicated to the late Gothic and the first Renaissance. There is a statue called Madonna col Bambino by Baboccio da Piperino (15th century) and a big Crocifisso made of polychrome wood made by an unknown author belonging to the first half of the 15th century. 

Room IV shows works of Antonello and of the Flemish and “Antonellian” culture: the polittico that Antonello painted in 1473 for the monastery of San Gregorio, made of five boards: La Madonna del Rosario in trono, San Gregorio Magno, San Benedetto and, on the top, Angelo and Vergine Annunziata. 

Room V hosts the works of Girolamo Alibrandi and works from the first part of the 16th century. Found here is the board called Giudizio Universale, dated 1514, and S. Caterina d’Alessandria and Presentazione al Tempio, signed by Alibrandi and dated 1519, found after the earthquake in 280 pieces. In this room are the marble ciborio of the Cathedral and the marble statue called Madonna col Bambino, both made by Antonello Gagini. 

Room VI is dedicated to the mannerist culture. In this room is a large painting called Adorazione dei pastori by Polidoro da Caravaggio, dated 1533, and, in the middle of the room, the original Scilla, made by Giovanni  Angelo Montorsoli. 

In room VII, it is possible to admire some showcases with some vasi da farmacia (vases used by chemists) and some pieces of jewelry of the 16th and 18th century. On the walls, some works are attributed to the artists of the second half of the 16th century.  

Room VIII hosts the statue of Francesco Maurolico, made by an unknown author of the 16th century. 

Room IX guards some paintings belonging to the first half of the 17th century, made by Alessandro Allori, Giovan Simone Comandè and others.
 Room X shows works of Caravaggio and painters of his school, The Raising of Lazarus (Risurrezione di Lazzaro) and the Adoration of the Shepherds (Adorazione dei pastori), two wonderful paintings made by Michelangelo Merisi from Caravaggio during his stay in Messina in 1609.
 Rooms XI and XII are dedicated respectively to the 17th and 18th century cultures, with works of the painters Giovan Battista Quagliata, Agostino Scilla, Giovanni Tuccari, Letterio Paladino and others.