Sexual dimorphism observed in autoimmune disease (increased in females) and cancer incidence (reduced in females) is proposed to be the result of mismatch between an ancestral environment (being pregnant near constantly) and modern environment (contraception and reduced pregnancies), and is mediated by evolution of the sex chromosomes. Itis proposed that, ancestrally, in a tit-for-tat with this fetal-induced dampening, the maternal immune system had to up-regulate to maintain a sufficient immune response to survive typical environmental attacks. However, in the absence of near-constant pregnancy, and dampening of the maternal immune system, the immune system of modern industrial women is prone to being hyperactive. Given the tremendous role of the immune system in surveying and preventing cancer, we propose that, while this “undampened” immune response may lead to detrimental autoimmune disease, it can also be protective against cancers in women.