The film, which Kidman will also produce, is based on the true story of Danish artists Greta and Einar Wegener, the world's first post-op transsexual.
Their marriage took a sharp left turn after Einar (Kidman) stood in for an female model that Greta (Theron) was set to paint.
When their portraits become wildly popular in 1920s Copenhagen, Greta encouraged her husband to adopt the female guise.
What began as a harmless game led Einer to a metamorphosis and landmark 1931 operation that shocked the world and threatened their love.
Both actresses won an Oscar playing lesbians – Charlize for her role as serial killer Aileen Wuornos, and Nicole for her role in The Hours – so the new movie won't be unchartered territory for the super-talented pair.
NICOLE KIDMAN PHOTOS