Because the clinical impact of cancer genomics is being increasingly recognized, tumor sequencing will likely continue to expand in breadth and scope. Therefore, it is vital for laboratory professionals to adopt the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists guidelines and create a standardized system of classification and nomenclature for somatic variants. Combining robust bioinformatics pipelines with thorough data analysis is necessary to efficiently and reproducibly identify and assess the impact of clinically relevant variants.