The analysis of fine-needle aspirates and effusions has proved to be a valuable tool for the cytological identification of metastatic melanoma. Nevertheless, while malignant pigmented cells can be easily detected on cytological specimens, their identification may be very difficult in patients bearing amelanotic lesions. In the present study we have evaluated whether this limitation can be overcome using two monoclonal antibodies (mAbs) HMB45 and Ep1-3, which are highly specific for the melanocyte lineage. These reagents were assayed in immunocytochemical tests performed on cytological material obtained from 50 patients with a past history of melanoma and 463 bearing metastases from a cryptic primary tumour. These mAbs, employed in combination with a panel of monoclonal reagents with well-defined tumour specificity, may improve the accuracy of the conventional cytopathological diagnosis of melanoma metastases in the two groups of patients.