- Has an eidetic memory. He can look at a script and he remembers what the pages look like. As he films a scene, he "reads" the page. The only reason he screws up a line is if very similar words (e.g. "it" and "is") are written fairly close together.
- He was working as a janitor at a rehearsal studio run by acting teacher & casting director Trent Gough in Times Square when he landed his first feature film Endless Love (1981).
- Has very poor eyesight, and cannot wear contact lenses. Has said that in roles in which he does not wear his eyeglasses, he can barely make out the face of the actor across from him in the scene.
- Loves cooking and is an excellent chef.
- Is quick to point out that, unlike the sleazy, sneaky characters he is best known for playing, he is actually a nice, friendly man in real life.
- Refuses to watch any of the movies he has appeared in.
- Is known to prefer being called "Jimmy".
- The birth date on the "Ten Most Wanted" poster for Raymond "Red" Reddington on The Blacklist (2013) in February 7, 1960, Spader's actual birth date.
- Has two sons: Sebastian Spader (born 1989) and Elijah Spader (born 1992).
- First performer to win Leading Drama Actor Emmy Awards for portraying the same character (Alan Shore) on two different series (The Practice (1997) and Boston Legal (2004)).
- Has appeared with Andrew McCarthy in three films: Pretty in Pink (1986), Mannequin (1987) and Less Than Zero (1987). McCarthy would later direct Spader in multiple episodes of The Blacklist (2013).
- Was close friends with John Kennedy Jr., both having attended Phillips Academy (Andover) high school together. Spader even dined occasionally with John Jr. at his mother Jacqueline Kennedy's Upper East Side apartment in New York.
- Good friends Christian Clemenson, Robert Downey Jr., Eric Stoltz, Jason Alexander, Rowdy Herrington and Andrew McCarthy.
- Greatly admires the work of Charles Laughton.
- His wife, Victoria Spader, was the set decorator for Sex, Lies, and Videotape (1989).
- Did commercial voice-overs for Acura car commercials.
- Fiancée Leslie Stefanson gave birth to his third son, Nathaneal, on August 31, 2008.
- He has English, with small amounts of Scottish, French, Dutch, German, Swiss-German, Norwegian, Welsh, and Irish, ancestry. Many of his family lines trace back to Colonial America of the 1600s. Among James's famous ancestors are Laurent Clerc, an educator of the deaf, who was born in La Balme, Cremieu, Isere, France; mathematician Nathaniel Bowditch, Revolutionary War general Joshua Babcock, and Paul Mascarene, a Lieutenant-Governor of Nova Scotia. James also shares a common "Vanderbilt" ancestor with famous businessman Cornelius Vanderbilt.
- Parents are Stoddard Greenwood and Jean (Fraser) Spader, both educators.
- His father died two weeks before he began production on Critical Care (1997).
- Has appeared with Eric Stoltz in four films: A Killer in the Family (1983), The New Kids (1985), 2 Days in the Valley (1996) and Keys to Tulsa (1997).
- He does not own a computer.
- Auditioned for the role of Cadet Captain Alex Dwier in the drama film Taps (1981), but eventually lost to Sean Penn.
- Has two unsuccessful television pilots, Diner (1983) and Starcrossed (1985), to his credit.
- He loves wine.
- Is a huge fan of the immortal Bob Dylan.
- Ex-son-in-law of Lee Kheel.
- Born on the same date (February 7, 1960) as Saturday Night Live (1975) "TV Fun House" writer/cartoonist Robert Smigel, best known as the voice of Triumph the insult comic dog from Late Night with Conan O'Brien (1993).
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