A number of preliminary research findings collected in our laboratory begins to suggest that silibinin can exert also STAT3-independent regulatory effects on key genes involved in the promotion and maintenance of cancer stem cells (CSCs) self-renewal during metastatic dissemination as well as in the immune active inflammatory microenvironment [56, 57], which may eventually produce additive or even synergistic anti-BM effects when combined with other therapeutic strategies. This evidence concerns the gene STAT3 and cancer.