Biomarkers become more and more important tools in clinical diagnosis of cutaneous malignancies. Furthermore, after vigorous validation, biomarkers may have influence on future prognostic classification systems. Clinical and histopathological parameters such as anatomic site, type of the primary tumor, tumor size, invasion depth, ulceration, vascular invasion, lymph node involvement and others are well established for their prognostic value. Additionally, an increasing variety of molecular markers have now been identified and described, providing a potential powerful platform for a more precise diagnosis and a more accurate prognostic sub-grouping of tumor entities. This might lead to future changes in existing classification systems, and might have consequences for the treatment and outcome of skin cancer patients. Recently published gene expression or proteomic profiling data relate to new marker molecules involved in skin cancer pathogenesis, which may, after validation by suitable studies, represent future prognostic or predictive biomarkers in cutaneous malignancies. The aim of this report is to summarize the currently known serologic and newer immunohistochemical biomarker molecules in the most common cutaneous malignancies malignant melanoma, squamous cell carcinoma, and cutaneous lymphoma, particularly emphasizing their prognostic and predictive significance.