Understanding cancer is fundamental to fighting the disease. However, in the past few decades, we have seen extensive pre-clinical and clinical studies of liquid biopsy (LB) and the more common clinical use of LB in daily practice. Some clinicians are skeptical about LB due to its non-standardized analysis techniques and protocols. They insisted on using solely tissue biopsy (TB) in the diagnosis of cancer patients. Therefore, we feel the need to give a perspective on the shifting paradigm from TB to LB, which is important to understand along with the recent development of liquid biopsy. Here, we briefly reviewed the known techniques for TB such as open biopsy (OB), core needle biopsy, and fine needle aspiration biopsy (FNAB), and their advantages and disadvantages. Furthermore, we reviewed the three main components analyzed in LB: circulating tumor cells (CTC), circulating tumor DNA (ct-DNA), and exosome, along with their enrichment and detection techniques. We also explained the clinical application of these three components in different solid tumors. The purpose of this chapter is to provide a clear explanation on the shifting paradigm of solid tumor biopsy: from TB obtained from the patient’s primary tumor to LB obtained from the patient’s bodily fluid, as well as the future perspective of LB.