Chronic inflammation has long been associated with the development of cancer, ever since Rudolf Virchow's first observation that leukocytes were present in neoplastic tissue more than 130 years ago. Recent evidences have reignited the interest of cancer researchers in the exciting concept of an association between chronic inflammation and cancer. Tumor necrosis factor alpha (TNF-alpha), initially discovered as a result of its antitumor activity, has now been shown to be one of the major mediators of inflammation. Induced by a wide range of pathogenic stimuli, TNF-alpha induces other inflammatory mediators and proteases that orchestrate inflammatory responses. TNF-alpha is also produced by tumors and can act as an endogenous tumor promoter. The role of TNF-alpha has been linked to all steps involved in tumorigenesis, including cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis. How TNF-alpha acts as a masterswitch in establishing an intricate link between inflammation and cancer is the focus of this review.