Stipe formed Single Cell Pictures with Sandy Stern in 1994 and landed a deal with New Line that same year. While that alliance proved basically fruitless, their next deal, a two-year development pact with October Films would lead to several important projects, as well as merge his music and film careers with a feature that included an additional partnership with Warner Bros., to produce and distribute, in association with the film company, Single Cell Pictures soundtrack albums. Single Cell's first notable film credit was Todd Haynes' stylized tribute "Velvet Goldmine" (1998), a glam rock fairy tale starring Jonathan Rhys Meyers, Christian Bale and Ewan McGregor. Both visually and thematically out of the ordinary, but with a decidedly celebratory feel, "Velvet Goldmine" had the spirit of pop music as well as being about pop music, and proved a smooth initial transition from music to film for Stipe. Single Cell's next venture, "Being John Malkovich" (1999) was also linked to Stipe's music background, as it marked the feature directorial debut of famed music video director Spike Jonze (who helmed R.E.M.'s "Crush With Eyeliner" in 1995). The film was irreverent, inventive and bizarre, in much the same spirit as early experimental punk music, oft-touted by Stipe as the pinnacle of scrappy creativity. With these two large-scale movies under the belt of Single Cell Pictures, the future of the production company looked promising. As of early 2000, in the pipeline were the fact-based drama "A Mystery of Cloth" and the experimental ensemble piece "Thirteen Conversations About One Thing". Single Cell even endeavored to branch out into television, showing the increasing fluidness of the entertainment industry as musician-producer Stipe collaborated with actors-turned-producers Robby Benson and Karla DeVito on an untitled pilot for a series set behind the scenes in the music industry.
While Stipe has had featured cameos (most memorably as bristly ice cream man Captain Scrummy in Nickeodeon's 1999 special "The Adventures of Pete and Pete: What We Did On Our Summer Vacation") and has proved a capable actor in R.E.M.'s later, more narrative music videos, he has been careful to point out that his interest in film lies strictly behind the camera. Nevertheless, he racked up big screen appearances in the 1987 short "Arena Brains" and the 1996 feature "Color of a Brisk and Leaping Day", as well as starring as himself in Peter Care's R.E.M. concert documentary "Road Movie" (1996) and as one of the cultural icons featured in Shainee Gabel and Kristin Hahn's documentary "Anthem" (1997).