This retrospective study sought to evaluate the impact of IL-6 concentration on time to progression in advanced melanoma. One hundred and thirty-five patients were included, serum IL-6 levels were determined before (Day 0), at the end of the treatment (Day 49) and at recurrence: the relationship between IL-6 concentration and time to progression (TTP) was also evaluated. The baseline median serum IL-6 level was 16.5 pg/ml. When disease progression was observed, an increase in serum IL-6 level was noted. In order to establish the possible relationship between IL-6 level and TTP, patients were divided into two groups (low and high) using the median IL-6 level (16.5 pg/ml) detected in the pretreatment serum of overall patients as a cut-off. Sixty patients were in the low IL-6 group and 56 patients in the high IL-6 group. Time to progression was calculated from the beginning of treatment to recurrence, and analyzed using the Kaplan-Meier method. Patients with low IL-6 serum concentration showed a significantly (p<0.00001) higher median TTP than patients with high IL-6 level. Patients maintaining a low IL-6 level during the treatment showed the longest median TTP compared with those supporting high levels (24.4 versus 5.5 months). Taken together, our results showed that serum IL-6 level could be considered a predictive marker of recurrent disease in metastatic malignant melanoma.