The clinical course of malignant melanomas is frequently unpredictable, although a number of prognostically useful variables can be identified. There is a need for additional markers of prognostic value. In a series of 60 malignant cutaneous melanomas, we analysed the immunohistochemical expression of c-myc proto-oncogene, heat shock protein 70 (HSP70) and HLA-DR molecules in order to investigate their prognostic significance. C-myc, HSP70 and HLA-DR were expressed in 43.3%, 56.6% and 38.3% of all melanoma cases, respectively. Advanced Clark levels (Clark III-V) were significantly associated with c-myc expression rate (P < 0.05), HSP70 detection (P < 0.01) and HLA-DR positivity (P < 0.01). Increased Breslow thickness (> 1.5 mm) was related to HLA-DR expression (P < 0.05). High mitotic rate was closely associated with c-myc positivity (P < 0.05), while HSP70 and HLA-DR expression separately correlated to clinical stage of the disease (P < 0.05). The evaluation of these variables may be of immunological and prognostic significance. They were found to be associated with melanocyte subpopulations of the vertical growth phase which are arguably characterized by an increased invasive potential.