The distribution of the extracellular matrix (ECM) glyco-protein tenascin (TN) has been evaluated immunohistochemically in benign and malignant lesions of the melanocytic lineage. Results of our study show that TN is detectable in a variety of benign and malignant lesions. In primary melanomas, TN displays a heterogeneous distribution, and a higher degree of expression of this glycoprotein is seen in lesions of greater dermal invasiveness. TN expression does not correlate with that of other ECM glycoproteins such as fibronectin. In vivo and in vitro experiments have also demonstrated that melanoma cells are capable of producing and releasing TN in the extracellular milieu.