Despite advances in our knowledge of the disease, malignant melanoma remains an unpredictable entity. The revolution in molecular biological techniques, such as DNA sequencing and gene-expression profiling, has uncovered many potential protein targets and biomarkers relevant to melanoma progression. Successful clinical application would be aided significantly by downstream proteomic validation of those candidate markers using a combination of immunohistochemistry and tissue microarrays. Yet, research in this context seems to lag behind the output of genomic data relating to melanoma. In this article, we look at the strengths and pitfalls of tissue microarrays in malignant melanoma. We will show how tissue microarrays have become a vital step in the transition from molecular techniques to useful clinical assays and interventions and look at likely future developments for advances in this field.