- Publisher Summary Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystem disease with distinct clinical and laboratory features. The etiology of the disease remains unknown. However, various hormonal, genetic and environmental factors have been implicated in the pathogenesis of SLE. Cardinal features of the disease include: B lymphocytes activation, the production of a wide variety of autoantibodies, the generation of pathogenic autoantibodies and their idiotypes, and the formation of immune complexes with the development of immune mediated tissue damage. The disease mainly affects females, suggesting a significant role of hormonal factors in the development of the disease. Recent studies have recognized malignancy as a significant contributor to the mortality and morbidity of this disease. This chapter focuses on the association between SLE and cancer. The chapter describes four studies to compare the risk of cancer among SLE patients with the general population. The studies have shown that patients with SLE have an increased risk of hematologic malignancies i.e., lymphoproliferative and hematopoietic malignancies. Several patients also develop solid tumor cancers including, lung, breast, gastrointestinal, and gynecological. The chapter discusses the four possible causes of cancer among SLE patients: the use of cytotoxic agents, a common etiologic agent, similar genetic susceptibility, and immunoregulatory disturbances of B and T cells in patients with SLE that predisposes to malignancy.