Investigators suspect that the theft, which took place at the Béziers Art Museum last Thursday afternoon but was only announced this week, was carried out to order.
De Chirico’s 1926 Composition with Self-Portrait had been on display in Béziers as part of the private collection of French Resistance hero Jean Moulin, who was born in the town.
Only the empty frame was left behind, according to France's Midi Libre, which said that the art museum does not have security cameras either inside or outside.
The painting is “priceless”, according to local prosecutors investigating the theft. De Chirico’s works have sold for millions of euros in the past, including one early painting owned by designer Yves Saint-Laurent that fetched €11 million at auction.
Given how famous the stolen work is, thieves will have difficulty selling it on any legal market, the Béziers town council said in a statement.
De Chirico was born to Italian parents in Greece. He helped found the Metaphysical movement in the early 20th century and is considered a major influence on surrealist artists across Europe.
He died in Rome in 1978, having rejected his early style and adopted far more traditional techniques. He remains most famous for his Metaphysical works, which can now be found on display in France, Britain, the United States and Italy, including at his former apartment in Rome.
De Chirico's Song of Love, owned by the Museum of Modern Art in New York.