Wadler has been treated for both breast and ovarian cancer. In 1991, aged 43, Wadler was diagnosed with breast cancer and had a malignant tumor "the size of a robin's egg" removed from her left breast. The eventual diagnosis was "ductal carcinoma with medullary features". Due to somewhat early detection and aggressive treatment, Wadler called it "[m]y maybe-not- the-best-but-still-pretty-terrific-whatever-the-hell-it-is cancer".

Her memoir about breast cancer, My Breast: One Woman's Cancer Story (ISBN 0671017756; ISBN 978-0671017750) was originally a two part cover story for New York Magazine and later expanded into an award-winning book and made into a television movie starring Meredith Baxter, which won the American Women in Radio and Television Excellence in Programming Award in 1995.

Wadler was later also diagnosed with "advanced ovarian cancer" and treated. She is working on a book about her experience with ovarian cancer, tentatively titled Plucky Cancer Girl Strikes Back.