The clinical significance of serum S100 was assessed in comparison to neuron-specific enolase (NSE) in 126 patients with malignant melanoma: 80 patients with clinical stage I/II, 23 patients with stage III and 23 patients with stage IV according to the criteria of the American Joint Committee on Cancer (AJCC). Using cut-off values of 0.15 microgram/l for S100 and 12.5 micrograms/l for NSE, the sensitivity was found to be 1.3% (1/80) for S100 and 8.75% (7/80) for NSE in patients with stage I/II, 8.7% (2/23) for S100 and 13% (8/23) for NSE in patients with stage III, and 73.9% (17/23) for S100 and 34.8% (8/23) for NSE in patients with stage IV disease (P < 0.05). In 6 patients with stage III/IV tumours, serial measurement of serum S100 and NSE was performed. A rise of serum S100 indicated progression of the disease; a decline indicated response to treatment. Our preliminary results support the value of serum S100 as an adjunct to the clinical staging and monitoring of metastatic malignant melanoma.