Next generation sequencing(NGS), massively parallel or deep sequencing are related terms that describe a DNA sequencing technology which has revolutionised genomic research. With the advent of NGS, cancer genomes can now be systemically studied in their entirety, an endeavour ongoing via several large scale cancer genome projects around the world, including a dedicated skin cancer genome project. This may provide many benefits including a more precise diagnosis and classification of the disease, more accurate prognosis, and potentially the identification of ‘drug-able’ causal mutations. Currently pilot projects are underway using NGS of cancer genomes in clinical practice, mainly aiming to identify mutations in melanoma that can be targeted by mutation-specific drugs. In our case, a 75-year old woman complaint abnormal hemorrhage in the urine continuously and finally diagnosed urethral melanoma. Lymph node metastasis was observed, stage 4 melanoma, operation was impossible. We performed NGS for genetic analysis of primary urethral melanoma. NGS was performed in urethal melanoma tissue, the primary lesion. Significant genetic abnormalities were observed in BRAF, TP53, TET2, and VHL. Several pilot studies of Meloma's NGS has been reported, and this case is thought to be a lessonable example of information that can be used to provide targeted therapy through NGS in rare and difficult surgical situations such as primary urethral melanoma.