Known for having detailed her long battle against the disease, the author was admitted into hospital on Monday as part of her ongoing treatment, a family spokesman said.
"Zoleka passed away... surrounded by friends and family," said Zwelabo Mandela.
She was the child of Mandela's youngest daughter, Zindzi Mandela, and her first husband, Zwelibanzi Hlongwane.
The family said recent scans revealed "significant" progress in the cancer that affected her hip, liver, lung, pelvis, brain and spinal cord.
"We mourn the loss of a beloved grandchild of Mum Winnie and Madiba," the Nelson Mandela Foundation wrote on social media, using the name by which the Nobel Peace Prize laureate was fondly known.
"Her work in raising awareness about cancer prevention and her unwavering commitment to breaking down the stigma surrounding the disease will continue to inspire us all."
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