Milan prosecutor Francesco Greco said an investigation had been opened following the death on March 1 of Moroccan-born Imane Fadil at one of the city's hospitals.
The 33-year-old had been brought to the hospital on January 29 with unexplained stomach pains.
Fadil was one of the witnesses who testified at the trial of the former Italian premier and media mogul on charges of having sex with an underage prostitute at one of his notoriously hedonistic bunga-bunga parties.
According to Italy's Corriere della Sera daily, the hospital had run a battery of tests to determine the cause of her failing health, but finding nothing, had sent off samples to a specialised laboratory in the northern town of Pavia.
The results came back on March 6, five days after her death, suggesting the presence of "a mixture of radioactive substances which are not normally available for purchase", the paper said, citing unnamed sources.
Fadil's lawyer, Paolo Sevesi, said she had spoken to him about "her fear of having been poisoned," the AGI news agency reported.
The former model first hit the headlines in 2012 when she gave detailed testimony about the goings on at Berlusconi's orgiastic parties at his villa in Arcore near Milan.
She testified that the first time she went to a party, she saw two young women in nun costumes stripping in front of the then prime minister. Later, she said he himself handed her 2,000 euros ($2,600) in cash, telling her: "Don't be offended."
Berlusconi has faced a string of charges over the so-called Rubygate scandal linked to his parties and the underaged prostitute Karima El-Mahroug, also known as "Ruby the heart-stealer".
Now 82, the billionaire businessman is currently on trial for paying a witness to give false testimony about his parties.
Berlusconi is already being investigated or prosecuted for witness tampering in Milan, Sienna, Rome and Turin, each time for allegedly paying people to keep quiet about his bunga-bunga parties.