Stitches begins with six-year-old David Small drawing pictures in his living-room floor in Detroit in 1951. Drawing is one of his two ways of expressing himself in an uncommunicative family—the other is getting sick. David's dad is a radiologist whose home medical treatments include injections, enemas, and chiropractic adjustments. The most damaging "medicine" he uses to treat his son's asthma is X-rays, which he administers at the hospital where he works.
David survives an early childhood punctuated by parental neglect and a scene of outright abuse by his mentally ill grandmother. One night, when he's eleven years old, his mother hosts a bridge club meeting, and a sophisticated neighbor named Mrs. Dillon attends. She notices that David has a growth on his neck and makes his mother promise to take him to a doctor (besides his dad). Mrs. Small's response is not concern, but rather annoyance at David for ruining her party.
His parents ignore his condition for three years, but finally, when David is fourteen, he has surgery to remove the growing tumor on his neck. It turns out to be cancer, but nobody tells David. Instead, the doctors remove one of his vocal cords, so when he wakes up from surgery, he's unable to speak.
David fades away during his adolescence, unable to relate to his peers and participate in their social life. He begins to act out, and when he goes on a joyride in his parents' car one night, the police arrest him for driving without a license. His parents send him off to a Christian boarding school, from which he repeatedly runs away.
Not knowing what to do with him, and refusing to just talk to him (though they do finally admit he had cancer), David's parents send him to therapy. There, for the first time, someone tells David the truth. His therapist, depicted in the book as the White Rabbit from Alice in Wonderland, tells David that his mother doesn't love him. While this might be harsh, it's the beginning of David's freedom.
Two things happen to make David leave home for good: He catches his mom in bed with Mrs. Dillon, and his dad confesses to having given him cancer with the X-rays. He moves into a rundown boarding house, which has no heat and holes in the floor, but it's better than living with his parents.
His artwork is his ticket out of Detroit, and the adult David is working as an art professor in upstate New York when he gets the call that his mother is dying. He goes to the hospital to say goodbye to her, screaming in his car the whole way there—not out of grief, but in order to strengthen his one remaining vocal cord.
The book ends with a dream in which David sees his mother sweeping the path to the mental institution where his grandmother died. She motions for him to come inside, but David refuses, choosing to break free of his family's troubled legacy.