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This review presents the first comprehensive synthesis of CPC biology, with a particular focus on the mechanisms governing their generation under physiological conditions and the distinct pathways that drive their formation within tumor microenvironments. We further summarize the broader clinical relevance of CPCs as potential biomarkers across infections, autoimmune diseases, and plasma cell disorders. With the rapid advancement of liquid biopsy technologies, CPC detection has garnered increasing attention in clinical practice. Here, we evaluate current and emerging methods for CPC detection, highlighting their respective advantages and limitations. 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