The myth of giants as first inhabitants of countries is a common legend shared by different cultures.

In this paper, we highlight that one of the determining factors of the origination of the myth was the discovery of large vertebrate bones (largely Cenozoic), initially interpreted as the remains of giant humans.

Thus, huge skeletons were interpreted by authoritative writers such as Strabo, Philostratus and Pliny (just to name a few) as the bodies of the mythological giant Antaeus, Ilio son of Hercules, Orestes, Cyclops and many others.

As for the myth of the Great Flood, also the hypothesis of the giants found a convenient literal confirmation in the Sacred Scriptures.

One of the first correct interpretations takes place in the first half of the eighteenth century with the studies of Hans Sloane which applied some rudiments of comparative anatomy to prove that the bones belonged to large cetaceans or terrestrial quadrupeds.

In the Italian panorama, until the eighteenth century, several authors were convinced of the past existence of entire nations of giants, which represented the first populations of Mediterranean islands.

Sloane’s work had a great impact also in Italy, although some ‘sacs of resistance’ persisted up to mid-nineteenth century. Isabella Salvador is thanked for providing photographic material. The ‘Sacro Bosco di Bomarzo’ is warmly thanked for allowing the use of photographic material in this paper.

The research was partially supported a financial received by M.R. from the Alexander von Humboldt-Foundation (Sofja Kovalevskaja-Award to Jörg Fröbisch ‘Early Evolution and Diversification of Synapsida’ of the German Federal Ministry of Education and Research).