Ras oncogene expression of malignant melanoma and melanocytic nevus have been immunohistochemically analyzed on formalin-fixed and paraffin-embedded tissues from 26 melanomas and 24 melanocytic nevi with a monoclonal antibody that was generated against Harvey sarcoma virus-derived ras oncogene products (p21ras). We found distinct differences of p21ras expressions by the type of melanoma. Nodular melanoma, epithelioid cell type melanoma, and deeply invading melanoma revealed higher reactivity with anti-p21ras monoclonal antibody than the other types. The reactivity of melanomas appeared to correlate with the degree of malignancy of the melanoma. It was also demonstrated, however, that part of melanocytic nevi reacted with anti-p21ras monoclonal antibody with a relatively strong intensity. Melanocytic nevi with junctional activity and nevus cells located in the epidermis in compound nevi did not show the positive reaction in contrast to dermally located nevus cells that had relatively strong reactivity. The different p21ras expression among the type of tumors may represent the state of tumor cells differentiation with greater expression with more immaturity in the melanocyte lineage. p21ras expression does not appear to represent a marker of malignant transformation.