Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule, member of the immunoglobulin gene superfamily that seems to participate in the evolution of the metastatic process. We investigated the significance of baseline soluble ICAM-1 levels on the outcome of patients with small-cell lung cancer and whether soluble ICAM-1 is a predictive marker for objective response during and after chemotherapy in patients with small-cell lung cancer. Fifty patients with recently diagnosed small-cell lung cancer, as well as 27 healthy smokers, were enrolled. Blood samples were collected at the time of diagnosis, during and at the end of chemotherapy. Data were correlated with the characteristics of the patients and survival as well as with ICAM-1 predictive role for objective response. Statistical significant values of baseline soluble ICAM between patients and controls (p < 0.001) were observed. Multivariate analysis revealed an elevated risk of death of 9 % in the first year after diagnosis for every 10 units of increased soluble ICAM-1 at the baseline (p = 0.046). Performance status and disease stage were also independent prognostic factors. Patients with extensive disease who achieved an objective response during chemotherapy showed a significant decrease (25.8 %) in their soluble ICAM-1 levels compared with baseline levels (p = 0.001). Alongside performance status and disease stage, baseline soluble ICAM-1 could be evaluated as an additional prognostic factor in patients with small-cell lung cancer. Also, a possible role for soluble ICAM-1 may exist as a predictive marker for objective response during chemotherapy for patients with extensive disease (p = 0.001).