Caveolins are the principal protein component of caveolae, plasma membrane invaginations found in most cell types. Caveolin-1 (Cav-1) plays a major role in oncogenesis through its various functions in lipid transport, membrane trafficking, and signal transduction. Increased expression of Cav-1 in tumor cells has been associated with aggressiveness and poor survival. More recently, loss of stromal Cav-1 expression was linked to poor survival and increased metastatic potential in breast and prostate cancer. To date, there is no study addressing the clinical significance of Cav-1 expression in malignant melanoma (MM). Our study consisted of 44 cases of MM: 12 MM lymph node metastases from patients with short survival, 12 MM lymph node metastases from patients with long survival and 20 primary MM. All cases were stained with Cav-1 antibodies. Cav-1 expression in melanoma and stromal cells was quantified using a 3 point scale: 0 = no staining, 1 = diffuse weak staining or strong staining in < 30% of cells, and 2 = diffuse strong staining. A score of 0-1 represented low Cav-1 expression and a score of 2 represented high Cav-1 expression. In patients with MM lymph node metastases, a low stromal Cav-1 expression was associated with shorter survival when compared to the high stromal Cav-1 expression group (median survival 252 days versus 3,508 days, p value 0.0054). Conversely, high Cav-1 expression in melanoma cells was associated with a longer survival in primary MM (p < 0.0001). In conclusion, high expression of stromal Cav-1 correlates with longer survival in malignant melanoma metastases, and high expression of Cav-1 in melanoma cells correlates with longer survival in primary malignant melanoma.