Next-generation sequencing (NGS) has revolutionized dermatopathology by enabling comprehensive genomic profiling of skin tumors. Its high-throughput capacity allows simultaneous analysis of multiple genes and pathways, providing unprecedented insights into the molecular mechanisms driving cutaneous neoplasms. This review summarizes current evidence on the application of NGS in cutaneous pathology, focusing on its diagnostic, prognostic, and therapeutic implications across major categories of skin tumors, including melanocytic, non-melanocytic, and adnexal neoplasms. In melanoma, NGS has defined molecular subtypes based on key driver mutations (e.g., BRAF, NRAS, NF1, KIT) and revealed distinct genetic pathways corresponding to etiologic and morphologic variants. In non-melanoma skin cancers, such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, NGS has elucidated the pivotal roles of PTCH1 and SMO mutations, UV-induced TP53 alterations, and viral oncogenesis, respectively. In adnexal tumors, NGS has uncovered recurrent gene fusions—such as YAP1::MAML2, MYB::NFIB, ETV6::NTRK3, and EWSR1::PBX3—defining novel molecular subsets with diagnostic and therapeutic relevance. NGS has profoundly enhanced the molecular understanding of cutaneous neoplasms, enabling refined tumor classification, biomarker discovery, and personalized therapy development. As sequencing becomes increasingly integrated into routine diagnostics, it is expected to transform the future of dermatopathology by bridging morphology and genomics toward precision medicine.