BACKGROUND 5-S-cysteinyldopa (5-S-DC) is a precursor of melanin. Its serum and urinary level can reflect melanoma progression. In this study we examined the concentration changes of 5-S-CD in melanomas of different clinical stages and in patients with different symptoms of melanoma, during and after treatment. METHODS Serum samples were taken from 252 melanoma patients on 765 occasions, from June 1996 to July 1998. Levels of 5-S-CD were determined by HPLC. RESULTS The value of 5-S-CD in patients with primary melanoma and in patients without symptoms ranged around the normal level. There was a significant difference between the values of patients with or without symptoms. There was also a significant difference between the 5-S-CD values at clinical Stage I and Stage III, as well as at clinical Stage II and Stage III, respectively. Analysing the values of patients with symptoms we found a significant difference between the mean values of primary tumour and stage III, between values in lymph node metastasis and stage III, between values in lung metastasis and stage III. The tumour burden was found to correlate with a rising marker level. In 7% of the symptomatic patients that had a marker level under the upper limit, amelanotic primary tumour was detected. CONCLUSIONS According to the high marker level in lung and liver metastases, the marker might be useful in monitoring both patients with disease free ocular melanomas, to detect liver metastasis and high-risk patients after surgical removal of the primary tumour to reveal lung metastases.