The play opens with three characters coming out to address the audience. Matilde comes out first, telling an elaborate joke in Portuguese without translation. Next Lane, a doctor in her 50s, comes out to explain that Matilde, her Brazilian maid, is depressed and has been failing to clean her house and so she had her medicated. She is followed by Virginia, Lane's older sister, a housewife, who argues that people who do not clean their own homes are insane. Matilde finally comes back on stage to tell the audience, this time in English, about how her parents, both wonderful comedians, recently died. Not knowing what to do with herself after, Matilde came to America to clean this house.
Lane and Matilde are still trying to work out their situation, especially since Lane feels uncomfortable having to order Matilde around and Matilde does not seem to be cleaning. While Lane is at work, Virginia comes to visit Matilde, having heard about her depression. Matilde explains that she doesn't like to clean and Virginia offers to clean the house for her every day before Lane comes home from the hospital.
Matilde and Virginia discover panties in Lane's laundry that look too sexy for her and begin suspecting her husband Charles, also a doctor, is cheating on her. Their suspicions are confirmed when Lane tells them that Charles has left her for an older woman named Ana, a patient of his who had breast cancer and is now recovering from a mastectomy. Lane deduces that Virginia has been cleaning the house instead of Matilde. Lane fires Matilde. Right before Matilde's departure, she sees Lane's imagined idea of Charles and his lover. She tries to tell Lane a joke, but as it is in Portuguese, Lane can't understand it. She tries to laugh, but just ends up crying. Virginia then enters to tell the two that Charles and Ana are at the door. The act ends with Charles calling to Lane from offstage.
The second act begins with Ana, a free-spirited Argentine, and Charles, who are the same actors who have been playing Matilde's parents during act 1. Charles performs surgery on Ana and then they act out the scene where they meet for the first time and fall in love in a matter of moments. The play then deposits the characters back to where act 1 ended, as Ana and Charles are let into the house awkwardly. Ana and Matilde bond immediately. Charles tells Lane that Ana is his Bashert (soul mate) and that, according to Jewish law (although neither he nor Lane is Jewish), this means that their marriage is dissolved. Lane doesn't know how to react, though she is clearly upset and bitter about the turn of events. Ana, after learning Matilde was just fired by Lane, offers for Matilde to come and clean their house. Lane, taking her aggression out on Ana, argues that she relies on Matilde and couldn't bear to part with her. Matilde, now being fought over by the two women, decides to split her time between both of their houses. Charles, Ana, and Matilde leave to go apple picking.
Matilde and Ana converse in Portuguese and Spanish on Ana's balcony, eating apples and throwing them into the 'sea,' which also happens to be Lane's living room. Meanwhile, back at Lane's house, she and her sister fight, with Lane taking out her frustration over the situation on Virginia's obsessive cleaning.
Ana and Charles fight over her going back to the hospital. Charles wants her to fight her cancer more aggressively, with Ana refusing to subject herself to more hospitals. Matilde watches as the two react to Ana's illness in their separate ways. While standing alone on Ana's balcony, Matilde discovers her 'perfect joke' and realizes that it did not kill her after all.
Soon, Matilde arrives back at Lane's home with news that Ana's cancer has come back and that she refuses to go to a hospital. She tells them that Charles, frantic for his lover's health, has gone to Alaska to cut down a Yew tree, which supposedly has healing powers. Matilde manages to convince Lane to visit Ana in a medical capacity. While at Ana's home, Lane examines Ana with an air of coldness before breaking down and yelling at her for making Charles love her in a way he never loved Lane. The two women share a moment, and Lane manages to forgive Ana