Current reports suggest serum S100 as a prognostic marker for disease progression in advanced malignant melanoma. In this study, we assessed serum levels of S100 and multiple clinical factors in relation to overall survival in 99 patients with metastatic malignant melanoma seen at our institution between May 1990 and April 1996. For statistical analysis, we used both univariate and multivariate Cox proportional-hazards models. Elevated serum levels of S100 correlated with poor outcome in metastatic malignant melanoma (P < 0.0001), univariate analysis). Upon multivariate analysis, however, S100 added no information to known clinical prognostic parameters.