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Due to the high morbidity and mortality of the coronavirus disease 2019 (COVID-19) in patients with malignancy, the necessity of vaccination in this group of patients became particularly important. Although a large number of studies have reported the safety of COVID-19 vaccination in multiple myeloma (MM) patients, the effect of the COVID-19 vaccine on MM relapse has not yet been reported. Here, we report a case of a possible association between relapse of MM and COVID-19 vaccination with Sinopharm®, an inactivated virus vaccine, in a patient with MM who has remained in complete remission for about 4 years. The MM relapse in the patient was diagnosed by both clinical findings and laboratory workup including serum protein electrophoresis, bone marrow aspiration, and biopsy. Despite this possible association between COVID-19 vaccination and MM relapse in the patient, given its importance in reducing mortality and having an acceptable safety profile, the COVID-19 vaccine should be administered to all cancer patients. However, careful monitoring and follow-up are recommended in patients with MM after COVID-19 vaccination.