"I can no longer serve the citizens in the manner that I have during the past six years," Blanchard said in a statement.
Blanchard's resignation is effective June 17.
Herb Williams, Blanchard's spokesman and close friend, said this afternoon, "His two doctors told him there is nothing more they can do (about the cancer) and he has contacted a hospice."
Blanchard, 70, has never publicly disclosed details about his cancer. The Santa Rosa City Council recently granted Blanchard a 60-day leave of absence in preparation for another round of chemotherapy. Blanchard had taken two previous leaves for health reasons.
Williams said Blanchard has since decided not to undergo the chemotherapy.
Blanchard was elected to the City Council in 2002 and re-elected in 2006. He has served as mayor since December 2006.
"I wish to thank the council members and staff for their understanding and support during the past two years. I am also overwhelmed by the generosity and well wishes from so many in the community," Blanchard said in his statement.
Williams said the City Council can appoint someone to complete Blanchard's term or put the seat up for election on the November ballot. Four other council seats are on that ballot.