Genodermatoses are rare genetic disorders with a broad spectrum of cutaneous and extracutaneous manifestations that have a genetic background. A thorough clinical examination, laboratory workup and morphological analyses of the skin remain crucial for the diagnosis in the era of next generation sequencing (NGS). The diagnostic algorithm depends on the clinical and molecular heterogeneity and should be adapted for each group of genodermatoses. In cases with uncharacteristic phenotypes which cannot be classified, NGS-based testing accelerates the time to diagnosis and leads to the identification of new disorders and new disease-associated genes. The new knowledge on genotype-phenotype correlations should enable revision of the classification of genodermatoses on a molecular basis.