I read with great interest the report by Lee and colleagues, illustrating the development of tumor lysis syndrome (TLS) following thalidomide (Thalomid ® ; Celgene Corporation, Warren, NJ, http://www.celgene.com) treatment in a patient with advanced hepatocellular carcinoma (HCC). To my knowledge, this is the first reported case of TLS with thalidomide in any solid tumors. Thalidomide has an unpredictable toxicity profile and poorly understood mechanisms of action. Under physiologic conditions, it is a racemic glutamic acid analogue consisting of S(-) and R(+) enantiomers that interconvert. In addition, it can be degraded into 20 different products, all with different mechanisms of action. Unfortunately, this characteristic cannot be invoked to explain the multiplicity of toxicities and anticancer effects associated with the drug. Thalidomide might exert its therapeutic properties through its antiangiogenic activity and modulation of cytokines, including tumor necrosis factor-α, interferon, interleukins 10 and 12, cyclooxygenase-2, and nuclear factor κB. Because of the concern for unpredictable toxicity in individual patients, we elected to use a lower starting daily dose of thalidomide, at 200 mg, in our study, allowing intrapatient dose escalation if tolerated. This may explain, at