The 50-year-old filmmaker and actor was deeply affected by the death of comedian Drake Sather, who took his own life in 2004.
Sather - who was an Emmy-nominated television writer and stand-up comedian - was well known for his work on The Larry Sanders Show and Saturday Night Live.
Yet his legacy has become the Blue Steel-wielding character he created: Derek Zoolander.
"He was the guy who really invented the character," Stiller said of Sather, who he worked with closely on the first film and developed a friendship with.
"He had an incredibly sardonic sense of humour. He was really smart, loved fashion, so for me it will always be missing something because he's not a part of it.
"But I also think it's kind of his legacy because he created the character."
Stiller, who was out it in Australia to celebrate the release of Zoolander 2, dedicated the sequel to the comedian.
Although almost two decades down the track, the Tropic Thunder star said he hopes Sather would have enjoyed the follow up.
"You know Drake ... I hope he would like it.
"What I always think is that I feel really good about what the movie is, but I know it would be even funnier if Drake had been writing on it."
Zoolander 2 has been received warmly by fans and critics alike, with much of the original cast returning including Will Ferrell, Owen Wilson and Christine Taylor along with new additions Penelope Cruz, Kristen Wiig and Benedict Cumberbatch.
Yet the film has not been without its controversies, with Cumberbatch's character drawing ire from trans activists.
"I think there's very real issues in the transgender community that people have been talking about over the last couple of years and I think that's important that's going on," said Stiller.
"I would say it's (Zoolander 2) in no way meant to mock the transgender world at all and that's it.
"I wouldn't say anything else or try to convince anyone of anything: I'd just say see the movie and judge for yourself."
