Before the construction of the Heleneum, the site was occupied by Villa Caréol which was built in the second half of the nineteenth century by Johann Frederic Häflinger from Bern. The villa was then sold to Oscar Bolz who was living in Castagnola at that time. He sold the property in 1929 to Hélène Bieber, a native of Frankfurt who lived in Paris. Mrs Bieber wanted to transform the villa into an elegant and international cultural salon, but the economic crisis of the 1930s put an end to her dreams.  Indeed, the house was almost always uninhabited and Lady Bieber usually stayed at Villa Castagnola or at the Hotel Splendide when she was in Lugano. 

In the beginning, Hélène Bieber did not want to rebuild the villa, but simply to renovate and enlarge Villa Caréol. Together with the architect Hugo Dunkel she however decided to demolish Villa Careol and to build a new and larger villa, which she called the Heleneum. The design of the Heleneum was inspired by the “Petit Trianon” in Versailles (1762-1768), built in the neo-classical style which was very much in vogue from the second half of the eighteenth century to the second half of the nineteenth century.

The building process faced  difficult phases: there were many different architects and due to the economic crisis of the 1930s, the project had to be downsized.   Lady Bieber moved to Castagnola and her arrival from Paris on 2nd of February 1934 is in fact recorded in the communal register. Before her death on the 23rd of December 1967, she donated her patrimony to five different charitable institutions. The authorities of the City of Lugano and Castagnola decided to buy the Heleneum in co-ownership. For many years the Heleneum's destiny remained uncertain. 

Just as Queen Marie Antoinette’s initials (M.A.) were emblazoned above the small stage where she had performed at the Petit Trianon, Helen Bieber’s initial (H) can been seen in the wrought-iron gate and fence on the Heleneum grounds.

Between 1969 and 1971 the Heleneum hosted piano master classes under the artistic direction of Carlo Florindo Semini,  Arturo Benedetti Michelangeli and Franco Ferrara. The Istituto Ticinesi di Alti Studi (Ticino Institute of Higher Education Studies) was later housed at the Villa.  The Insitute was directed by Elémire Zolla and gathered archaeologists, anthropologists, art historians, philosophers, linguists, Egyptologists and Orientalists under the same roof. 

Between 1971 and 1976 the Heleneum was the headquarters of the Istituto Dalle Molle that worked on artificial intelligence, and organised seminars in collaboration with the Istituto di studi semantici cognitivi (ISSCO) (the Institute of Semantic Cognitive Studies), which were attended by researchers from Europe and the rest of the world. In the early 1980s the villa was used for film shoots which included the actors Bruno Ganz and Aldo Fabrizi.

In 1988, after Serge Brignoni’s donation, the City Council of Lugano approved the municipal suggestion to use the Heleneum as the home of the Museo delle Culture Extraeuropee (Museum of Extra-European Cultures), which later became the Museo delle Culture (Museum of Cultures). 

The museum offered guided tours of the garden and the villa (by appointment only). The Villa has hired as a venue for meetings and special events.