The Class II alpha helical family of cytokines now includes the extended Interleukin-10 family (IL-10, IL-19, IL-20, IL-22, and IL-26) as well as the closely related Interferon-a, Interferon-γ, and Interferon-τ (1–22). The importance of the distaff side of this family, the interferons (22,23), for cancer biology and tumor immunology has been well defined since the initial report of substances interfering with viral infection by Isaacs and Lindenmann almost 50 yr ago (25–27). Less clear, evolving, and more ambiguous has been the role of the IL-10 extended family defined in the last 15 yr, many of them with more interferon-like properties (22). In cancer patients with malignant melanoma (28), ovarian cancer (29), and other hematologic malignancies such as, lymphoma (30) and multiple myeloma (31), IL-10 itself can be identified in the serum and/or tumor. Indeed, a negative correlation between circulating levels of IL-10 and prognosis has been reported. For this reason, IL-10 was suspected to be produced by tumor cells, followed by suppression of antitumor immune responses. IL-10 may also act as a tumor growth factor. For example, exogenous IL-10 administration causes expansion in a number of melanoma cell lines owing to the expression of IL-10 receptor (32). In contrast, IL-10 produced by some activated immune cells can promote antitumor activity and is indicative of a potent antitumor immune response. Thus, elevation of IL-10 levels does not always correlate with prognosis in patients with cancer, reflecting its complex biology.