For several decades, a strong link between oncology and autoimmunity has been unveiled, and autoantibodies that are found in patient sera during tumorigenesis have emerged as exciting, alternative blood-based biomarkers that may aid in early cancer diagnosis. This chapter summarizes current autoantibody-based immunoassays, as well as previous and ongoing research in the space of diagnostic autoantibody discovery and validation, for the six most commonly diagnosed cancers globally, including breast, lung, colorectal, prostate, non-melanoma, and melanoma skin and gastric cancer. Other novel uses of autoantibody immunoassays in oncology are also discussed at the conclusion of this chapter.