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Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P= 3× 10− 4), Breslow thickness (P= 5× 10− 10), ulceration (P= 9. x10− 8) and mitotic rate (P= 3× 10− 7), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95% CI 1.13-2.83), as previously reported …