All cancers are diseases of the genome, since the cancer cell genome typically consists of 10,000s of passenger alterations, 5-10 biologically relevant alterations, and 1-2 "actionable" alterations. Therefore, somatic mutations in cancer cells can have diagnostic, prognostic, and predictive value. Traditional methods are widely used for testing, such as immunohistochemistry, Sanger sequencing, and allele-specific PCR. However, due to the low throughput, these methods are focused exclusively on testing the most common mutations in target genes. The modern next generation sequencing (NGS) is a technology that enables precision oncology in its current form. ESCAT and ESMO Guidelines defined NGS for routine use in patients with advanced cancers such as non-squamous non-small cell lung cancer, prostate cancer, ovarian cancer, and cholangiocarcinoma. The high sensitivity of the NGS method allows it to be used to search for specific mutations in circulating tumor DNA in blood plasma and other body fluids. NGS testing has evolved from hotspot panels, actionable gene panels, and disease-specific panels to more comprehensive panels. The exome and whole genome sequencing approaches are just beginning to emerge, that is why panel-based testing remains most optimal in oncology practice. NGS is also widely used to identify new and rare mutations in cancer genes and detect inherited cancer mutations.