Pelosi's line in the sand is sure to please the Democratic base and AARP, both of which oppose raising the Medicare age.
But it could put her at odds with President Obama, who was reportedly open to the idea last summer.
Congressional Democrats are walking a fine line on the issue as the so-called "fiscal cliff" looms.
A number of Democratic leaders — including Pelosi — have said they would support certain Medicare cuts, but they don't want benefit reductions to be a part of the talks.
Pelosi last month said she would judge any final package by its balance between cuts and revenues, but also strongly suggested she would draw the line at entitlement benefit cuts like raising Medicare's eligibility age.
"I don't know what they are saying by structural [changes]. Is that a euphemism for 'I am going to cut your benefit if you are a middle‑aged senior?' Is that what structural change means? No, I don't support that."
Rep. John Larson (Conn.), the outgoing chairman of the Democratic Caucus, delivered a similar message this month.
"Where's the fairness in the wealthiest nine-tenths of 1 percent still not doing their fair share while we exact that out of people who are in need of Medicare and Medicaid?" Larson asked last week. "It's a fairness argument, it always has been, and that's what it will continue to be."
On Tuesday, House Minority Whip Steny Hoyer (D-Md.) emphasized that everything – including cuts to benefits in Medicare and Social Security – should be on the table, but he hinted that he might not support them as part of a final deal.
"I agree that everything's on the table, but that doesn't mean we're for everything," he said, adding that "some of" the ideas Republicans have floated "are not advisable."
"We need to protect and strengthen Social Security and Medicare," he said.
— Mike Lillis contributed