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Although several molecules have been evaluated as tumor markers of malignant melanoma (MM) progression, there are few available markers sensitive enough to detect recurrence or metastasis. The objective of the present study was to determine clinical significance of serum soluble adhesion molecules in the monitoring of progression in patients with MM. Serum levels of soluble L-selectin (sL-selectin), sE-selectin, sP-selectin, and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by ELISA in 57 MM patients. In a retrospective longitudinal study, nine serum samples from two MM patients were analyzed during a follow-up period of 4.0 and 4.3 years, respectively. Serum sICAM-1 levels in MM patients were significantly higher than those in healthy controls and tended to be elevated as the disease stage progressed. In contrast, serum sL-selectin levels were significantly lower in MM patients compared to healthy controls and tended to decrease as the disease stage progressed. There was no significant difference in serum sE-selectin and sP-selectin levels between MM patients and normal control. In a longitudinal study, increased sICAM-1 and decreased sL-selectin levels were generally associated with the progression of MM. These results suggest that monitoring both sICAM-1 and sL-selectin is available to evaluate the progression of MM.