Loss of expression of E-cadherin, the major cell-cell adhesion receptor on keratinocytes, has been linked to tumour progression in various carcinomas. As E-cadherin has been reported to be expressed in cultured human melanocytes, we questioned whether loss of E-cadherin expression may also be related to melanocytic tumour progression. Flowcytometrical analysis demonstrated that E-cadherin was expressed on cultured normal melanocytes and naevus cells. Two non-invasive, non-metastatic melanoma cell lines showed low expression, and four invasive, metastatic melanoma cell lines did not express E-cadherin. Immunohistochemistry on frozen sections of human melanocytic lesions resulted in diffuse staining of 1/23 common naevocellular naevi and 1/13 dysplastic naevi, with no staining in any of seven early primary melanomas (< or = 1.5 mm). Staining was observed in 4/20 advanced primary melanomas (> 1.5 mm) and 5/35 melanoma metastases. Thus, even though E-cadherin is expressed in cultured melanocytes and naevus cells and lost in invasive, metastatic melanoma cells in vitro, it is rarely found in early stages of melanocytic tumour progression in situ and, surprisingly, some expression can be observed in 10-20% of lesions of advanced stages.