Up to 10% of all cancers may be caused by inherited genetic changes. The prevalence of cancer paired with the decrease in sequencing costs and improved NGS data quality is driving the growth of the hereditary cancer testing as it is important to implement surveillance and risk-reduction strategies, detect cancer at an early, more treatable stage, and provide tailored treatment and therapies. Panels are often designed to cover dozens of genes and performing validation and assessing performance requires samples with common mutations in each of those genes. Biosynethic reference materials can address these challenges. Here we describe the development and multisite evaluation of Seraseq Inherited Cancer DNA Mix v2, which contains genes recommended for testing by the American College of Medical Genetics, the National Comprehensive Cancer Network, and the American Society of Clinical Oncology.