Sir Harpal Kumar, chief executive of Cancer Research UK, is to stand down in the spring after more than 10 years in the role.
A CRUK spokesman for the charity said Kumar would take some time to decide his next career move.
Kumar was appointed chief executive of Cancer Research Technology, a wholly-owned subsidiary of CRUK, in 2002 before becoming chief operating officer of the parent charity in 2004. He has been chief executive of CRUK since April 2007.
Kumar, who was knighted in the 2016 New Year Honours list for services to cancer research, said in a statement today he "always believed that organisations benefit from refreshed leadership every so often and CRUK is no exception".
CRUK is the UK's largest fundraising charity and had an overall income of £679.2m in the year to the end of March 2017.
A statement from the charity said it had made significant strides in the fields of cancer prevention and early diagnosis under Kumar’s leadership.
Sir Leszek Borysiewicz, chair of CRUK, said: "I would like to thank Harpal for his tremendous contribution to the charity over the past 15 years. CRUK is a truly remarkable organisation and even more so because of Harpal's inspirational leadership."
He said the charity had begun the search for Kumar’s successor and planned to make an appointment to coincide with his departure.