The Hepatitis A (HAV), B (HBV), C (HCV), and E (HEV) viruses are the most common causes of acute and chronic liver disease, which is a major source of morbidity and mortality worldwide. Currently, real-time PCR assays are routinely used to ensure the rapid detection and quantification of these viruses; however, the accuracy and reproducibility of these assays are limited by the lack of precisely quantified control materials, which are essential for determining analytical specificity and sensitivity. To address this need, ATCC has developed synthetic quantitative molecular standards for HAV, HBV, HCV, and HEV that are compliant with ISO 13485, quantified via digital PCR, and validated with published qRT-PCR assays. In the following proof-of-concept study, the HAV, HBV, HCV, and HEV synthetic molecular standards were used to generate standard curves with published primer sets. Furthermore, the standard curves for HBV and HCV were used to quantify the 3rd WHO international standard for HBV and the 4th WHO international standard for HCV from the National Institute for Biological Standards and Control (NIBSC) via the same specific published assays.