The distribution of a recently produced melanoma specific antibody (HMB-45) has been evaluated histochemically on paraffin sections in a large panel of melanocytic and non melanocytic tumours. Results have been compared with the presence of S-100 protein. HMB-45 was shown to be a highly specific antibody being present only in melanomas, junctional melanocytes and histogenetically related neoplasms such as melanocytic neuroectodermal tumour of infancy and, at low levels, on a proportion of peripheral nerve sheath tumours. The high specificity of HMB-45 antibody, coupled with the greater sensitivity of S-100, makes the combined use of these markers practical in the differential diagnosis of skin tumours and of metastatic lesions of uncertain primary site.