"It is with immense sorrow that we report our client James Gandolfini passed away today while on holiday in Rome, Italy," said his managers in a statement.
"Our hearts are shattered and we will miss him deeply. He and his family were part of our family for many years and we are all grieving."
According to BBC News, the HBO TV network said Gandolfini died of a possible heart attack. He was reportedly set to attend a film festival in Sicily.
"We're all in shock and feeling immeasurable sadness at the loss of a beloved member of our family," HBO said in a statement. "He was special man, a great talent, but more importantly a gentle and loving person who treated everyone no matter their title or position with equal respect. He touched so many of us over the years with his humor, his warmth and his humility. Our hearts go out to his wife and children during this terrible time. He will be deeply missed by all of us."
Gandolfini won three Emmys for his role on the HBO series The Sopranos, which aired from 1999 to 2007 and helped establish the cable network. He was also recently in the film Zero Dark Thirty and was part of the Tony Award-winning Broadway comedy God of Carnage.
He worked as a bartender and a club manager before his acting career took off on Broadway in 1992.
His breakthrough role came a year later playing a mobster in the movie True Romance.
Gandolfini's more recent film credits included In The Loop and Killing Them Softly.
He is survived by his second wife, Deborah Lin, a former model from Hawaii, whom he married in 2008, and his son, Michael, from his first marriage to Marcy Wudarski, his former personal assistant. They were married in 1999 but separated three years later.
In a December 2012 interview with the Associated Press, Gandolfini said he had become an actor to get rid of anger.
"I don't know what exactly I was angry about," he said. "I try to avoid certain things and certain kinds of violence at this point. I'm getting older, too. I don't want to be beating people up as much. I don't want to be beating women up and those kinds of things that much any more."