In 2000, the main building re-opened, after years of renovation. The centerpiece of the Benaki Museum, it aims to present the historical and cultural development of Hellenism within its geographical and evolutionary context, from prehistory to the present.

The priceless collections housed in this building depict masterpieces from the Neolithic Age, the Antiquity and the Roman Era to the Byzantine Age, and from the fall of Constantinople, the period of Frankish rule and the Ottoman Occupation, to the outbreak of the Greek War of Independence in 1821. The collections also include works of art from the time of the formation of the Modern Greek State until the Asia Minor Catastrophe in 1922.

The breadth and variety of such collections defines the Benaki Museum and sets it apart, not as another historical museum, an art museum or a museum of decorative arts, but as the museum of Greek civilization, in all its manifestations.