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Objective: Conventional karyotyping of multiple myeloma (MM) is hampered by the low mitotic index of plasma cells (PCs), and low proportion of PCs in some specimens may lead to false negative results in fluorescence in situ hybridisation (FISH) detection., Methods: Bone marrow cells were cultured in an ordinary medium for 24 h or in a medium containing 10 ng/mL IL-6 and 40 ng/mL GM-CSF for 6 d. Fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION) was also conducted, combining CD138 fluorescent immunophenotype and FISH., Results: Under modified culture conditions, the successful rate of culture and abnormality detection rate during karyotype analysis increased to 86.4% and 40.9%, respectively. The abnormality detection rate of FICTION (89.5%) was significantly higher than that of FISH (60.0%). The genetic abnormality detection rate increased to 92.3% when FICTION and karyotyping were conducted under modified culture conditions., Conclusion: The established modified culture system could improve karyotyping quality in MM. Due to its obvious advantages compared with FISH, FICTION is recommended for detecting genetic abnormalities in MM., (Copyright © 2021 by the Association of Clinical Scientists, Inc.)