Activated intracellular signaling pathways based on mutations in oncogenes and tumor suppressor genes play an important role in a variety of malignant tumors. In dermatology, such mutations have been identified in melanoma, basal cell carcinoma and squamous cell carcinoma. These have partly led to the establishment of new, targeted therapies. Treatment successes have been particularly impressive for melanoma with small molecule inhibitors directed against the mutated BRAF oncogene and in basal cell carcinoma with inhibitors directed against the hedgehog signaling pathway. New sequencing technologies, in particular next generation sequencing, have led to a better and more comprehensive understanding of malignant tumors. This approach confirmed the pathogenic role of BRAF, NRAS and MAP kinase pathways for melanoma. At the same time, a series of further interesting target molecules with oncogenic mutations such as ERBB4, GRIN2A, GRM3, PREX2, RAC1 and TP53 were identified. New aspects have recently been shown for squamous cell carcinoma by detection of mutations in the NOTCH signaling pathway. A better understanding of the pathogenesis of these and other tumors should lead to improved and maybe even individualized treatment. The current developments in dermatological oncogenetics based on the new sequencing technologies are reviewed.