Zinc (Zn) is an essential heavy metal that is incorporated into a number of human Zn metalloproteins. Zn plays important roles in nucleic acid metabolism, cell replication, and tissue repair and growth. Zn deficiency is associated with a range of pathological conditions, including impaired immunity, retarded growth, brain development disorders and delayed wound healing. Moreover, many reports have suggested that Zn is involved in cancer development and levels of Zn in serum and malignant tissues of patients with various types of cancer are abnormal. Zn may directly affect tumor cells by regulating gene expression profiles and/or cell viability, both of which are mediated in part by tumor-induced changes in Zn transporter expression. On the other hand, Zn may indirectly influence tumor cells by affecting processes within the cancer microenvironment, including immune responses; the functions and/or activity levels of immune cells that attack tumor cells are influenced by the intracellular Zn concentrations within those cells. In both cases, Zn contributes to intracellular metal homeostasis and/or signal transduction in tumor and immune cells. In this review article, we will summarize the current understanding of the roles of Zn homeostasis and signaling primarily in immune cells, with a discussion of the contributions of these processes to oncogenesis. (Cancer Sci 2008; 99: 1515–1522)