We have previously shown that human metallopanstimulin (MPS-1) is a ubiquitous 9.4-kDa multifunctional ribosomal S27/nuclear "zinc finger" protein which is expressed at high levels in a wide variety of cultured proliferating cells and tumor tissues, including melanoma. In the present study, we have examined the expression of the MPS-1 protein in various types of human benign and malignant melanocytic lesions of the skin. The expression of the MPS-1 protein was studied by immunohistochemistry using specific anti-MPS-1 antibodies. We found that in benign nevi, the staining is weak and in a gradient; most often, only type A melanocytes stain positive. The B and particularly the C types are negative. Remarkably, congenital nevi show a similar gradient staining of regular benign nevi, but in addition one example showed intensely positive dermal nodules adjacent to areas of negative melanocytes. In melanomas, the staining patterns for MPS-1 are more complex. While some melanomas stain evenly and intensely positive, others have remarkably variable expression of MPS-1. The scattered melanocytes migrating to the upper layers of the epidermis are usually intensely positive. In summary, benign lesions stain in an orderly pattern with staining gradients that correlate with the cellular differentiation of the nevi. Malignant melanomas have an erratic, often intense staining that also correlates with the disorderly growth of these neoplasms. These differential results indicate that the MPS-1 antigen is a useful marker for melanocytic lesions at the immunohistochemical level.