Intriguingly, there is growing evidence that many tetraspanins such as CD151 and CD82 can negatively or positively influence tumor development and metastasis in oncogenic context- and cell lineage-dependent manners, where they regulate strength of cell-cell junctions, signal transduction of the Wnt pathway, the epithelial-mesenchymal transition (EMT), maintenance of cancer stem cells (CSCs), and dynamics of exosomes (Table 1) [20,21,28,33,34,35]. The gene discussed is CD82; the disease is cancer.