- Says that, of all the roles he has played in his career, Inigo Montoya from The Princess Bride (1987) is his absolute favorite.
- Fans of The Princess Bride (1987) frequently attend his live performances just to hear him utter the famous line, "My name is Inigo Montoya. You killed my father. Prepare to die." He frequently includes the famous line towards the series' ending.
- Has played the same character (Dr. Jeffrey Geiger) on three different series: Picket Fences (1992), Homicide: Life on the Street (1993) and Chicago Hope (1994).
- Had left cornea replaced due to degenerative eye disease (keratoconus). (November 1998)
- He is a lover/collector of Lionel model trains and he continues to enjoy playing with them to this day. He considers the concept of hanging on to such "classic" influential toys from the past very important to pass down to future generations.
- Briefly studied acting at New York's Juilliard School of Drama, but dropped out to pursue work.
- During an October 2019 interview with Rosanna Greenstreet in The (London) Guardian, Greenstreet asked Mandy Patinkin, "What is the worst thing anyone's said to you?" His answer was, "'I hate tenors and I hate Jews, but you moved me.' Said by an audience member who waited to meet me after a concert. I was horrified that a human being needed to couch a compliment in hate.".
- Began singing in the temple choir at age 9.
- Did an interview for a 1987 The Princess Bride (1987) featurette pretending to have worse English than the character he was playing (a Spaniard). In reality, he's American, born and bred.
- Mandy's mother, Doralee Patinkin Rubin, was a cookbook author.
- Portrayed a spirit from the 1950s in his first television commercial for 7-Up (1970). Also played the lead role in the very first television commercial for Kellogg's Frosted Mini-Wheats.
- Comes from a Jewish family (from Russia, Latvia, and Sokole, Poland).
- Occasional appearances on Late Show with David Letterman (1993) on CBS-TV. His most memorable performances were with Tony Randall, who accompanied him pretending to have had a taxi breakdown and therefore needing an emergency rehearsal hall. Mandy then brings down the house with Al Jolson standards "Swanee", "Mammy", etc.
- Mandy does concerts for the gun control advocacy group Pax and for Doctors Without Borders, a group that provides medical relief in violence-torn areas such as Darfur, Lebanon, and many other developing countries.
- Nominated for the 2018 Emmy Award in the Supporting Actor in a Drama Series category for his role as Saul Berenson in Homeland (2011), but lost to Peter Dinklage from Game of Thrones (2011).
- Won Broadway's 1980 Tony Award as Best Actor (Featured Role - Musical) for playing Ernesto 'Che' Guevara in Broadway's "Evita". He was also nominated twice as Best Actor (Musical): in 1984 for Broadway's "Sunday in the Park with George", a role he recreated on television Sunday in the Park with George (1986), and in 2000 for Broadway's "The Wild Party".
- Before he and Adam Arkin starred as doctors on the television show, Chicago Hope (1994), they both played doctors in the movie, The Doctor (1991).
- His father, Lester Patinkin, operated two large metal factories, the People's Iron & Metal Company and the Scrap Corporation of America, before he passed away from cancer.
- Attended the University of Kansas in Lawrence, Kansas for two years before being discovered.
- Had his right cornea replaced due to degenerative eye disease. (May 1997)
- He has appeared in one film that has been selected for the National Film Registry by the Library of Congress as being "culturally, historically or aesthetically" significant: The Princess Bride (1987).
- Was not asked to reprise his Tony Award-winning role of Ernesto 'Che' Guevara in the movie version of Evita (1996).
- He released a CD entitled "Kidults" featuring children's songs among others (2000).
- Acted in very first commercial for Kellogg's Frosted Mini-Wheats; commercial filmed in Chicago's Loop.
- Delivered the opening speech at the Annual Convention of the Israeli Left, where he recounts his experiences during a visit to the West Bank with Breaking the Silence members. (May 2012)
- He was awarded a Star on the Hollywood Walk of Fame for Television at 6243 Hollywood Boulevard in Hollywood, California on February 12, 2018.
- Attended and graduated from Kenwood High School in Chicago, Illinois (1970).
- Performed in the CBS Radio Mystery Theater's fourth episode, "Lost Dog" with Kim Hunter, broadcast on January 9, 1974.
- Surname is pronounced "PUH-ting-kin".
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