Massive parallel sequencing (MPS) technologies have paved the way into new areas of research including individualized medicine. However, sequencing of trace amounts of nucleic acids still remains a major challenge, especially for degraded nucleic acids like circulating DNA or RNA. This, together with high costs and time requirements, impedes many important applications of MPS in medicine and fundamental science. We have developed the “Capture and Amplification by Tailing and Switching” (CATS) method to generate ready-to-sequence DNA libraries from picogram amounts of either DNA or RNA molecules in a time frame of several hours, that permits sequencing of circulating nucleic from diagnostic volumes of liquid biopsies with unprecedented depth. CATS approach could find broad application in diverse research areas such as translational medicine including therapy monitoring, prediction, prognosis and early detection of various human disorders, and will permit high-throughput DNA sequencing from previously inaccessible material such as minute forensic and archeological samples.