The movie, which was officially confirmed during Paris Fashion Week last month, will see Stiller and co-star Owen Wilson reprise their roles as dim male models Derek Zoolander and Hansel McDonald.
Stiller announced Cruz's casting with this funny 'flashback' on Instagram.
"Excited to announce Penelope "Little Penny" Cruz has joined #Zoolander2 cast! #fbf (sic)," Stiller said of the 40-year-old actress' casting.
Will Ferrell, who played villain Mugatu in the original 2001 comedy, has also been linked to the project.
Filming on the sequel is thought to be heading to Rome soon, with the movie having been given a provisional release date of February 12, 2016.
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