M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was carried out to investigate the serum levels of M30 and M65 in patients with melanoma and the relationship with tumor progression and known prognostic parameters. Fifty-two patients with cutaneous melanoma were investigated. Serum samples were obtained on first admission before adjuvant and metastatic treatment were provided and at follow-up. Both serum M30 and M65 levels were determined using an enzyme-linked immunosorbent assay. The median age of patients at diagnosis was 54 years, range 16-88 years; 30 patients were men. Over half of the patients (58%) were in the metastatic stage and most (63%) had M1c. The baseline serum M65 levels were significantly higher in patients with melanoma than in the control group (P<0.001). For the serum M30 levels, no difference was found (P=0.76). Both the serum M30 and M65 levels were significantly higher in the patients with leukocytosis (P=0.02 and 0.007, respectively). In addition, the serum M30 levels were also elevated in young (P=0.02) and female patients (P=0.01). A significant relationship was found between the serum levels of M30 and M65 (r(s)=0.408, P=0.003, Spearman's correlation). As expected, distant metastasis (P<0.001), advanced metastatic stage (M1c) (P=0.03), elevated erythrocyte sedimentation rate (P=0.001), higher serum lactate dehydrogenase levels (P<0.001), and unresponsiveness to chemotherapy (P<0.001) had worse survival. However, neither serum M30 nor serum M65 had a significantly adverse effect on survival (P=0.23 and 0.68, respectively). In conclusion, although only serum M65 levels were found to be of diagnostic value, neither M30 nor M65 serum levels played a prognostic role in the outcome in melanoma patients. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.