The Ganoderma lucidum (Leyss. ex Fr.) Karst, an edible mushroom, has been utilized for centuries in East Asia to prevent or treat various diseases and to reduce the likelihood of cancer invasion and metastasis. The primary bioactive compounds are commonly considered to be polysaccharides and triterpenoids. Evidence that G. lucidum extract and its bioactive compounds may have a potential inhibitory effect on cancer invasion and metastasis is increasingly being reported in the scientific literature. This review assembles and summarizes past publications on the in vitro and in vivo effects of G. lucidum on cancer invasion and metastasis, and concludes that these effects occur through modulation of the phosphorylation of extracellular signal-regulated kinase (ERK1/2), phosphatidylinositol 3-kinase (PI 3-kinase) or Akt kinase (protein kinase B). Activation of these kinases subsequently inhibits the activity or expression of activator protein-1(AP-1) and nuclear factor-kappa B (NF-kappaB), resulting in the down-regulation of urokinase plaminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, interleukin (IL)-8, inducible nitric oxide (NO) and beta1-integrin as shown in various cell lines or animal models. G. lucidum may be an effective nutraceutical used in the prevention of cancer metastasis. To further elucidate the bioactive components present in G. lucidum and the anti-metastatic mechanisms underlying these compounds, more in vitro and in vivo tests as well as clinical trials are necessary.