Adiponectin, an adipocyte-secreted hormone that plays an important role in diabetes and cardiovascular disease, may also be of importance in the development and progression of several malignancies. Circulating adiponectin concentrations, which are determined mainly by genetic factors, nutrition, and adiposity, are lower in patients with breast, endometrial, prostate, and colon cancer. It has thus been proposed that adiponectin may be a biological link between obesity (especially central obesity) and increased cancer risk. Adiponectin may influence cancer risk through its well-recognized effects on insulin resistance, but it is also plausible that adiponectin acts on tumor cells directly. Several cancer cell types express adiponectin receptors that may mediate the effects of adiponectin on cellular proliferation. Herein, we review recent evidence supporting a role of serum adiponectin concentrations as a novel risk factor and possible diagnostic marker for obesity-related malignancies, including cancers of the breast, endometrium, colon, and prostate. Further studies are needed to fully elucidate the potential role of adiponectin in cancer diagnostics and therapeutics.