Madonna has lost her younger brother Christopher Ciccone to cancer at the age of 63.
He passed away on Friday after battling cancer, his representative told TMZ.com.
The designer and artist worked closely through much of her career, having acted as her personal assistant and dresser, interior decorator and artistic director of her tours, but their relationship was not without its ups and downs.
The pair were close throughout Madonna's rise and reign as the Queen of Pop, but fell out after their working relationship soured and he published information about their relationship in his 2008 book, Life with My Sister Madonna.
Christopher's death comes less than two weeks after the passing of their stepmother, Joan Clare Ciccone, who died on 24 September after her own battle with cancer.
He initially served as one of his sister's backup dancers before acting as show designer and backstage dresser, as well as eventually serving as the art director for her Blonde Ambition world tour, and as tour director for The Girlie Show. He also directed music videos for Tony Bennett and Dolly Parton.
They fell out over the 2008 book, but had made up by 2012, according to Christopher, who said they were in contact but were no longer working together.
Madonna, 66, is yet to publicly comment on the news.