Depository fat functions as endocrine tissue able to regulate whole-body energy homeostasis. Obesity and aging are independently associated with a deregulation of adipose tissue, resulting in pro-inflammatory status and excessive release of adipokines. These events are under investigation for a possible synergism in determining chronic diseases, including cardiovascular illnesses and several types of cancer. Our data, obtained through an observational study conducted with prostate cancer patients, confirmed the association of leptin, an adipose tissue-derived adipokine, with cancer, and suggested that serum leptin represents a stronger risk factor for prostate cancer (PCa) in older than in younger subjects. In elderly patients, visceral obesity measured by waist to hip ratio provided a better correlation with serum leptin in terms of body mass index (BMI) measurements and appeared to be a more adequate indicator for obesity. The expression of leptin receptor mainly observed in invasive prostate carcinoma tissue and in aggressive prostate cancer cell lines suggests a possible molecular link between persistently high leptin levels, seen in aged obese subjects, and PCa progression.