The secreted MIA protein is upregulated in melanocytic tumors and expression parallels the progressive malignancy of melanoma cells. Recent reports suggest MIA as a diagnostic tumor marker that may also serve as an indicator of tumor progression. In this study we evaluated the association between pre- and post-treatment serum levels of MIA and survival in 70 patients with advanced melanoma. Elevated (> or = 8.8 ng/ml) pre-treatment levels of MIA predicted a poor prognosis in these patients. Overall median survival in stages III and IV was 13 months in MIA positive patients, compared to 28 months in patients with negative pre-treatment MIA levels. The staging-related analysis showed a median survival of 14 months in MIA positive patients, versus 28 months in MIA negative patients in stage III, and 12, versus 19, months in stage IV melanoma, respectively. In addition, there was a trend towards a poorer survival in patients where MIA serum levels remained high after surgery. Therefore, determination of pre- and post-treatment serum MIA levels could be useful for the management and prognosis of metastatic melanoma patients.