- He was asked to audition for the role of Chandler Bing on Friends (1994), while he was doing a play in London. His reading was videotaped by a British casting agent but the tape failed to arrive in the United States before the network had made its final decision.
- Cryer's two front teeth are fake after having lost his two front teeth while diving into the shallow end of a swimming pool.
- Assumed temporary custody of his son, Charlie, after Charlie's mother, Sarah Trigger, was arrested in May 2009 on felony neglect charges. Charlie's two-year-old stepbrother was found with rope and cord marks around his neck.
- Attended Junior High School 104 with Robert Downey Jr.. He co-starred with him in the comedy movie Due Date (2010).
- He was awarded a Star on the Hollywood Walk of Fame for Television at 6922 Hollywood Boulevard in Hollywood, California on September 19, 2011.
- Received death threats via telephone while shooting Two and a Half Men (2003). (January 2010)
- Once an usher at the Equity Library Theater, where he was often mistaken for actor Matthew Broderick.
- His daughter, Daisy, was born on 11 August 2009; adopted by Jon and Lisa shortly after.
- He and his Two and a Half Men (2003) co-star Charlie Sheen also starred together in the parody movie Hot Shots! (1991).
- On January 23, 2007, he revealed his engagement to television reporter Lisa Joyner on The Tonight Show with Jay Leno (1992).
- Attended Junior High School 104 in New York City, with fellow actors Robert Downey Jr., Erica Gimpel and Kadeem Hardison.
- Son of David Cryer and Gretchen Cryer, Broadway actors.
- Attended and graduated from The Bronx High School of Science (aka Bronx Science) in New York City (1983).
- In the movie Pretty in Pink (1986), Cryer played his first notable role, a character called "Duckie". In 2015-16, he played a recurring character on NCIS (2003) called Dr. Cyril Taft, opposite David McCallum's character, Dr. Donald "Ducky" Mallard. At one point in the episode "Loose Cannons", (2016) Cryer, as Taft, says "That would be just ducky, Duckie. I've been dying to say that!".
- His first child with his wife Sarah Trigger, a son Charlie Austin, was born on 27 June 2000 in Los Angeles, California.
- Appeared, with Charlie Sheen, in a PSA for the "Wounded Warriors Project" (2009).
- Has played the same character (Lex Luthor) in four different series: Arrow (2012), The Flash (2014), Supergirl (2015) and Batwoman (2019).
- Has Dutch, English, German, Swiss-German, Scottish and Swedish ancestry.
- He was considered for the role of Chandler Bing on the sitcom Friends (1994), which went to Matthew Perry.
- Attended Stagedoor Manor Theatre Camp.
- Friends with Paget Brewster.
- Born on the exact same date as Martin Lawrence.
- Uncle of Gracie Hyland.
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