- Holds the record for being nominated for most Best Supporting Actor Emmys for a character, "Dr. Niles Crane" on Frasier (1993). He was nominated 11 times.
- One year when he was performing at the international comedy festival "Just for Laughs", he arrived in Montreal for check-in with the festival exhausted and disheveled. He remarked to one of the festival workers how he was looking forward to resting in his hotel room. The worker replied with empathy, saying how tired they were working overtime with few breaks trying to tie up the loose ends and help the performers before the comedy routines. Moments later, Pierce returned with fresh coffee and pastries for all those working at the Festival's check-in.
- He received his initial interview with the creators of Frasier (1993) due to his close resemblance to Kelsey Grammer. After the interview, the part of Niles Crane was written for him.
- Is active in the fight to find a cure for Alzheimer's, which his grandfather suffered and died from. His father also suffered from the disease but died from pneumonia.
- Attended Yale with Jodie Foster. When she was preparing to direct Little Man Tate (1991), she remembered him from a play he was in at that time and called and offered him a part.
- Asked not to be credited as the voice of "Abe Sapien" in Hellboy (2004) because he felt the characterization of Abe truly belonged to Doug Jones (the actor who played Abe on the set).
- Plays both the piano and the organ.
- Graduated from Yale University with a double major in English and theater arts.
- He kickboxes.
- Once worked as a security guard.
- He named his five favorite films as The Godfather (1972), Bonnie and Clyde (1967), Horror of Dracula (1958), Unfinished Piece for the Player Piano (1977) and A Midsummer Night's Sex Comedy (1982).
- Once sold ties at Bloomingdales in New York.
- Received the Yaddo Medal as best dramatic arts student upon graduation from Saratoga Springs High School, 1977.
- Companion of Brian Hargrove since the early '80s. David said in his Tony award acceptance speech in 2007 that he has been with Brian for 24 years. They moved together to Los Angeles (where they still live) in the early '90s.
- Has played Kelsey Grammer's brother twice: on Frasier (1993) and on Brother from Another Series (1997). John Mahoney also played the father of both pairs of characters.
- Pierce resides in Los Angeles with his longtime partner TV writer/director/producer Brian Hargrove.
- Has been selected to play "brave Sir Robin" in the Broadway production of "Spamalot," the musical version of "Monty Python and the Holy Grail," scheduled to open on Broadway in February, 2005. (July 2004)
- Made his debut with the New York Philaharmonic in April 2003 in the role of "Benedict", in the concert staging of Berlioz's opera "Beatrice and Benedict". Harriet Sansom Harris, (agent "Bebe Glazer" on Frasier (1993)) played "Beatrice" opposite Pierce.
- He and his husband have been outspoken in the media on the subject of legalizing gay marriage in America.
- He was awarded the 2007 Antoinette Perry (Tony) Award for Best Actor in a Musical for "Curtains" on Broadway in New York City.
- Attended Bethesda Episcopal Church in Saratoga Springs.
- He was nominated for a 1984 Joseph Jefferson Award for Director of a Revue for "Candida" at the Goodman Theatre in Chicago, Illinois.
- He was awarded the 2006 Back Stage Garland Award for Performance in a Musical for "Curtains" at the Ahmanson Theatre in Los Angeles, California.
- He is the son of Laura Marie (Hughes) and George Hyde Pierce. His paternal grandfather was born in Canada. David has significant Colonial American (English) ancestry, with deep roots in Massachusetts and Connecticut, as well as a Welsh-born maternal great-grandfather.
- He was nominated for a 1984 Joseph Jefferson Award for Actor in a Principal Role in a Play for "Candida" at the Goodman Theatre in Chicago, Illinois.
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