She was 40.
Mirzakhani' friend Firouz Naderi announced her death on Saturday on Instagram, and her relatives confirmed the death to the Mehr agency in Iran.
"A light was turned off today. It breaks my heart ..... gone far too soon," wrote Naderi, a former director of Solar Systems Exploration at NASA.
"A genius? Yes. But also a daughter, a mother and a wife," he added in a subsequent post.
Mirzakhani, a professor at Stanford University in California, died after the cancer she had been battling for four years spread to her bone marrow, Iranian media said.
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The award recognized her sophisticated and highly original contributions to the fields of geometry and dynamical systems, particularly in understanding the symmetry of curved surfaces such as spheres.
She had already won the 2009 Blumenthal Award for the Advancement of Research in Pure Mathematics and the 2013 Satter Prize of the American Mathematical Society.
Born and raised in Tehran, Mirzakhani initially dreamed of becoming a writer, but by the time she started high school her affinity for solving mathematical problems and working on proofs had shifted her sights.
"I felt that this was something I could do, and I wanted to pursue this path."
Mirzakhani became known on the international mathematics scene as a teenager, winning gold medals at both the 1994 and 1995 International Math Olympiads -- finishing with a perfect score in the latter competition.
In 2008 she became a professor of mathematics at Stanford. She is survived by her husband and young daughter.