European Parliament President David Sassoli died overnight, his spokesperson said early on Tuesday.
The Florence-born journalist-turned-politician was 65.
He died at an oncological centre in Aviano, in the northeastern province of Pordenone, after being hospitalized on December 26 with serious complications related to an immune-system dysfunction.
"I am deeply saddened by the terrible loss of a great European & proud Italian," said European Commission President Ursula von der Leyen via Twitter.
"David Sassoli was a compassionate journalist, an outstanding President of the European Parliament and, first & foremost, a dear friend.
"My thoughts are with his family.
"Riposa in pace, caro David! "Rest in peace David, my dear friend".
Italian Premier Mario Draghi hailed Sassoli as a "man of the institutions, a profound European, a passionate journalist".
"Sassoli was a symbol of balance, humanity, generosity," Draghi said.
"These qualities were always recognized by all his colleagues, of all political persuasions and of every EU country, which bears witness to his extraordinary civil passion, capacity to listen, (and) constant commitment at the service of citizens.
"His premature and sudden passing dismays us".
European Council President Charles Michel described Sassoli as a "sincere, passionate European".
"We already miss his human warmth, his generosity, his cordiality and his smile," Michel said.
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