Objective To improve the detection rate of cytogenetic abnormalities of monoclonal plasma cells through quality control cycle (QCC) activities. Methods A QCC team was established to collect the bone marrow samples of patients suspected with multiple myeloma, who undergoing plasma cell-associated fluorescence in situ hybridization (FISH) in Department of Hematology, Changhai Hospital of Navy Medical University (Second Military Medical University) from Jun. 2014 to Dec. 2014. The detection rate of cytogenetic abnormalities of monoclonal plasma cells was analyzed and compared with literatures to find out the difference and related causes, and then the improvement measures were formulated and practiced to evaluate the improvement effect. Results We found that low tumor load in the initial specimen and the detection result could not be judged due to that value is very close to the critical value were the two key points to be improved in the QCC activity. Based on the brainstorming and the existing laboratory conditions, the QCC team chose to sort abnormal cells by flow cytometry to increase tumor cell density and reduce background value before genetic testing. Finally, the detection rate of cytogenetic abnormalities of monoclonal plasma cells increased from 61.3% (95/155) to 92.1% (174/189) in our hospital. Conclusion The FISH detection process of bone marrow of patients suspected with multiple myeloma is optimized through QCC activities, and the detection rate of cytogenetic abnormalities of monoclonal plasma cells is effectively improved.