Leptin is a recently identified hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and body weight. A number of proinflammatory cytokines, such as interleukin 6, tumor necrosis factor alpha, and interferon gamma, have been proposed as mediators of cancer cachexia; these data suggest that abnormalities in leptin production/release or in its feedback mechanism play a role in cancer patients. We therefore studied the relationship between serum leptin and serum cytokines interleukin 6 and tumor necrosis factor alpha levels in advanced-stage cancer patients. Twenty-nine advanced stage cancer patients (all but one stage IV) with tumors at various sites were included in the study. A direct correlation between body mass index and serum leptin levels was found both in cancer patients and in healthy individuals. The serum levels of interleukin 6 were significantly higher in cancer patients than in healthy individuals. In cancer patients an inverse correlation was found between serum levels of leptin and proinflammatory cytokines. There was an inverse correlation between the Eastern Cooperative Oncology Group performance status scale and serum levels of leptin. Regarding survival, patients with very high serum levels of proinflammatory cytokines and very low levels of leptin had very short survival. Although obtained in a cancer patient population not overtly cachectic, our results provide further evidence that a simple dysregulation of leptin production and/or release cannot be involved in cancer-associated pathophysiological changes leading to cachexia.