- He was diagnosed with a benign brain tumor (more specifically, an acoustic neuroma) in 2002; he subsequently had it removed and is in good health.
- Bartended for nearly a decade while trying to break into show business.
- In an interview with Moviemaker magazine, he claims to have made 800 auditions in his lifetime before succeeding.
- He was set to appear in Signs (2002) but had to drop out when he was diagnosed with a brain tumor. His role in Signs (2002) went to Joaquin Phoenix. The brain tumor Mark was diagnosed with was found to be benign. Following brain surgery, he has fully recovered after suffering from a partial facial paralysis.
- Was close friends with Heath Ledger. He is also friends with Gael García Bernal.
- Became a father for the second time at age 37 when his wife Sunrise Coigney gave birth to their daughter Bella Noche Ruffalo in May 2005.
- His uncredited cameo as a snoozing Dr. Banner in Iron Man 3 (2013) makes him only the second actor - the first was Bill Bixby - to play the role twice.
- His brother, Scott Ruffalo, died December 8, 2008, after being found outside his Beverly Hills home after a gunshot wound to the head. He was a 39-year-old hairdresser and was married to Luzelena. His body was cremated.
- His father was a construction painter and his mother a hairstylist. His three siblings (Scott Ruffalo, Tanya Marie Ruffalo and Nicole Ruffalo) are all hairdressers.
- Like his predecessor and friend Edward Norton, he was a huge fan of the "Incredible Hulk" comics and television series before playing the title character.
- Became a father for the third time at age 39 when his wife Sunrise Coigney gave birth to their daughter Odette Ruffalo on October 20, 2007.
- He is an animal rights activist and anti-fracking activist.
- He was supposed to play the role of Perry Smith in Infamous (2006) but had other engagements and so recommended Daniel Craig, who then went onto get the job.
- Lives in ultra trendy Los Angeles neighborhood, Los Feliz. Giovanni Ribisi, Bo Barrett, Scarlett Johansson, Chris Pine, Ryan Reynolds, Brad Pitt, Kristen Stewart, Michael Cera, Hannah Telle and Robert Pattinson are among the other actors who also call Los Feliz home.
- His father is of Italian descent. His maternal grandfather was of French-Canadian ancestry, and his maternal grandmother was also of Italian descent.
- Benicio Del Toro was a fellow student at the Stella Adler drama school in Los Angeles, California.
- His son, Keen Ruffalo, was born in June 2001.
- He was Louis Leterrier's original choice for the title role in The Incredible Hulk (2008), but the studio wanted Edward Norton. Ruffalo was later cast in the role in The Avengers (2012) and has played the role since.
- While appearing in the drama "Awake and Sing!", he was nominated for the 2006 Tony Award (New York City) for Supporting or Features Actor in a Drama.
- For his environmental advocacy, Mark Ruffalo received a Global Green Millennium Award and a Meera Gandhi Giving Back Foundation Award. Also chosen as one of the "People Who Mattered" by Time magazine (2011).
- Studied at the Stella Adler Conservatory in Los Angeles, California.
- Sold his three-bedroom, 2,957-square-foot house in Los Angeles' Hollywood Hills for $1,650,000. He bought the property in 2004 for the same price for which he later sold it. He moved his family to Callicoon, New York. (2009)
- Attended and graduated from First Colonial High School in Virginia Beach, Virginia.
- He supported Bernie Sanders in the 2016 U.S. Presidential election.
- Was in attendance at Chris Penn's funeral at Holy Cross Cemetery in Culver City, California.
- He is well-known for his far left-wing political views and activism.
- Has worked with Gwyneth Paltrow in three films: View from the Top (2003), The Avengers (2012) and Thanks for Sharing (2012).
- He auditioned for the role of Doctor Doom in The Fantastic Four (1994) but was turned down.
- Has worked with Gwyneth Paltrow, Reese Witherspoon, Jennifer Garner, Scarlett Johansson, Kate Winslet, Jim Carrey, Kirsten Dunst, Keira Knightley and Bradley Cooper.
- He was awarded a Star on the Hollywood Walk of Fame at 6777 Hollywood Boulevard in Hollywood, California on February 8, 2024. Director David Fincher and Jennifer Garner were guest speakers at the ceremony. The Walk of Fame star is located in front of the Stella Adler Studio of Acting.
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