According to HBO and managers Mark Armstrong and Nancy Sanders, the actor died Wednesday while on vacation in Rome.
Dr. Claudio Modini, head of the emergency room at the Policlinic Umberto I hospital in Rome, said the actor suffered a cardiac arrest. He arrived at the hospital at 10:40 p.m. (2040 GMT, 4:40 p.m. EDT) Wednesday and was pronounced dead at 11 p.m. after resuscitation efforts in the ambulance and hospital failed, Modini said.
Modini told The Associated Press that an autopsy would be performed starting 24 hours after the death, as required by law.
Gandolfini is probably best known for his role as wiseguy Tony Soprano in "The Sopranos," which aired from 1999 to 2007. He won several Emmy awards and Screen Actors Guild awards for his work in the HBO drama about a troubled crime boss struggling to balance his career in the mafia and his family life.
"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. "
David Chase, creator of The Sopranos, called Gandolfini a "genius."
"He is one of the greatest actors of this or any time. A great deal of that genius resided in those sad eyes," Chase said in a statement. "I remember telling him many times, 'You don't get it. You're like Mozart.' There would be silence at the other end of the phone. For Deborah and Michael and Liliana this is crushing. And it's bad for the rest of the world. He wasn't easy sometimes. But he was my partner, he was my brother in ways I can't explain and never will be able to explain."
Gandolfini was a stage and film actor appearing in numerous films, including "Get Shorty," "Zero Dark Thirty" and "The Incredible Burt Wonderstone."
In 2007, Gandolfini moved behind the camera, helping produce the Emmy-nominated documentary special on HBO, "Alive Day Memories: Home from Iraq."
Born in Westwood, N.J., Gandolfini was introduced to acting as a young man living in New York City.