[6][12] While taking part in season 5 of Finding Your Roots with Henry Louis Gates, Jr., Notaro learned she is also a distant cousin of Gloria Steinem.

Her 2012 album, Live, is a recording of a stand-up set performed shortly after she was diagnosed with breast cancer.

In 2012, she appeared on Conan, and in May of that year on the live episode of This American Life, which was broadcast to theaters nationwide and on radio in edited form.

She performed a monologue about having encountered Taylor Dayne on multiple occasions, greeting her each time with, "Excuse me, I'm sorry to bother you, but I just have to tell you.

[21] In July 2015, a Netflix film, Tig,[22] chronicling her attempts to become pregnant with her fiancée, Stephanie Allynne, was also released.

[23] Singer Sharon Van Etten wrote a song in homage to Notaro called "Words" that is heard in the credits.

[24] In November 2015, Notaro co-wrote, produced, and starred in a semi-autobiographical TV pilot for Amazon Video called One Mississippi.

[26] It follows Notaro's character as she returns to her hometown of Bay Saint Louis, Mississippi after her mother's unexpected death.

[26] Her first stand-up one-hour special was released by HBO in 2015, Tig Notaro: Boyish Girl Interrupted.

[29] She was digitally inserted in post-production in Zack Snyder's Army of the Dead, replacing Chris D'Elia, who was accused of sexual misconduct.

[2] In the autumn of 2016, she appeared in a video as an onstage "stand-in" during the Nostalgic for the Present concert tour of Australian singer Sia for the song "Diamonds.

[38] On August 3, she addressed her cancer diagnosis and other personal difficulties during a live stage show at Largo in Los Angeles.

[41] Notaro subsequently had a double mastectomy with no reconstructive surgery;[45][46] she opted out of chemotherapy but decided instead to continue treatment with hormone blocking.

[49] In 2017, Notaro adopted a vegan diet, which she credited for eliminating the chronic pain she had experienced in the years following her cancer diagnosis.