Marchetto is best-known for the graphic novel/memoir (also published by Random House) she wrote about her 2004/2005 battle with breast cancer through her witty cartoon-panelled memoir titled Cancer Vixen: A True Story, which earned a Critics Choice recommendation from People. To make matters more difficult she had to go through her cancer treatments without health insurance, which she had allowed to lapse.

In one cartoon panel of Cancer Vixen she posits the following:

• "...[W]hat does 29 Needles + 18 pounds + 15 radiation technicians + 11 Medical assistants + 9 Nurses + 8 Doctors + $192,720.04 + 2 Rabbis + 1 Priest =?"
• "Answer: ...An Experience That Has Changed Me Forever."

Another set of panels show a female figure representing Marchetto arguing with the Grim Reaper as follows:

• "Listen Cancer, Ya Sick Bastard"
• "Finally, at 43, I'm Getting Married for the First Time"
• "And David Remnick, Editor in Chief of The New Yorker Wants to Publish More of my Cartoons"
• "NOW IS NOT A GOOD TIME!

Acocella Marchetto donates a portion of "Cancer Vixen" book sales to The Breast Cancer Research Foundation, and is the founder of The Cancer Vixen Fund at Saint Vincent's Comprehensive Cancer Center, which annually funds free mammograms for uninsured women in New York City.

Shortly after its release, "Cancer Vixen" was optioned by Cate Blanchett's Working Title Films.

On June 11, 2008, The CANCER VIXEN FUNd, which puts the FUN in FUNdraising, raised $150,000 for women who are uninsured so they can receive the best breast care. In total, The CANCER VIXEN FUNd, founded by Marchetto, has raised over $400,000 for the uninsured. To date Marchetto has raised over $1,000,000 for cancer research and women who are uninsured.