Cells with a dendritic morphology and/or expression of dendritic cell (DC) markers have been repeatedly described in several human tumors, but the distribution and density of melanoma-associated DCs have not yet been reported. The aim of the present study is to analyze the density and topographical distribution of melanoma-associated DCs and their relation with CD3(+), CD4(+) and CD8(+) T lymphocytes in forty cases of cutaneous human melanoma. In melanocytic tumours different pools of DCs were recognised in the epidermis and in the dermis, particularly in intimate relation with lymphocyte clusters inside the melanocytic proliferation, and more often at the edges of tumours. The number of Langerin-positive DCs showed an inverse correlation with tumour depth (correlation coefficient r= -0.59, P=0.0001) and was significantly lower in thick melanomas compared to thin and intermediate ones (P<0.0005). The density of CD83(+) DCs was significantly lower in thick melanomas compared to thin and intermediate ones (P<0.009). A significant correlation was found between the density of the two DCs subsets (r=0.57, p<0.0001). The number of CD3(+) lymphocytes was inversely correlated to the depth of infiltration (r=-0.596, P<0.0001): melanoma cases with II-III Clark level showed a higher T lymphocyte mean density compared to cases with IV-V Clark level (P<0.0001). T lymphocyte density was significantly lower in thick melanomas compared to thin and intermediate melanomas (P<0.0005). In conclusion, our study indicates a progressive loss of DCs and T lymphocytes in the neoplastic progression of melanomas; further identification of the molecular pathways involved in the functional impairment of these immunitary cells may lead to new immunotherapeutic approaches for melanoma patients that would improve the clinical outcome of the patients.