The company also said that "effective immediately," Thane Kreiner, vice president of corporate affairs, has been named senior vice president of marketing and sales.
Affymetrix said Siegel will be "transitioning from her current role" and will represent the company as president emeritus. Affy said she will stay on as an advisor and continue to report to Chairman and CEO Stephen Fodor.
It was not immediately clear why Siegel stepped down, whether the resignation takes immediate effect, or whether Kreiner's role will overlap her duties. Also not clear is whether Affy has begun looking for a replacement.
An Affymetrix spokesman said the company will "address these questions when we're ready, at the appropriate time."
Siegel joined Affymetrix in 1998 as senior vice president of sales and marketing -- the same title to which Kreiner was now promoted. Affy named her president in 1999 and appointed her to the board two years later.