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Their detection in peripheral blood is now feasible across the disease spectrum, from MGUS and smoldering myeloma to solitary plasmacytoma, symptomatic MM, and plasma cell leukemia, providing a dynamic window into tumor biology. Technological advances, including high\u2010sensitivity flow cytometry and next\u2010generation single\u2010cell sequencing, have enabled accurate enumeration and molecular interrogation of CTC. Beyond their biological significance, CTC quantification has consistently demonstrated independent prognostic value at diagnosis, with even low levels predicting inferior survival outcomes. Recent proof\u2010of\u2010concept studies, such as MinimuMM\u2010seq and SWIFT\u2010seq, established that genomic and transcriptomic profiling of CTC can recapitulate canonical myeloma lesions, reveal clonal heterogeneity and track evolutionary dynamics under therapy. 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Although methodological challenges remain\u2014particularly, standardization, sensitivity, and integration into clinical workflows\u2014CTC analysis holds the promise of transforming from a surrogate biomarker to a clinically actionable tool, advancing precision medicine in MM.<\/jats:p>","DOI":"10.1002\/ajh.70326","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:34:12Z","timestamp":1776130452000},"page":"1575-1588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Circulating Tumor Cells in Multiple Myeloma: From Peripheral Clues to Central Insights"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0616-8694","authenticated-orcid":false,"given":"Benjamin","family":"Podvin","sequence":"first","affiliation":[{"name":"Laboratory of Hematology Lille University Hospital  Lille France"},{"name":"PERSTIM Lab INSERM UMR\u2010S1277, Lille 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