This review discusses the immunological roles of 5 major mushrooms in oncology: Agaricus blazei, Cordyceps sinensis, Grifola frondosa, Ganoderma lucidum, and Trametes versicolor. These mushrooms were selected based on the body of research performed on mushroom immunology in an oncology model. First, this article focuses on how mushrooms modify cytokines within specific cancer models and on how those cytokines affect the disease process. Second, this article examines the direct effect of mushrooms on cancer. Finally, this article presents an analysis of how mushrooms interact with chemotherapeutic agents, including their effects on its efficacy and on the myelosuppression that results from it. For these 5 mushrooms, an abundance of in vitro evidence exists that elucidates the anticancer immunological mechanisms. Preliminary research in humans is also available and is promising for treatment.