BACKGROUND Focal segmental glomerulosclerosis (FSGS) very rarely occurs in patients with multiple myeloma. Much more common are renal impairments secondary to monoclonal light-chain tubulopathy, AL amyloidosis, light-chain deposition disease, and the so-called monoclonal gammopathy of renal significance. CASE REPORT We report the case of a 79-year-old myeloma patient without noticeable medical problems but with a long history of myeloma treatment beginning 13 years ago. In the ninth line of therapy, he was successfully treated with belamaf mafodotin, an anti-BCMA monoclonal antibody coupled to monomethyl auristatin F. After 1.5 years of treatment, without any eye toxicity, and while he was in complete hematologic remission, he experienced a very severe COVID-19 infection followed 1 month later by a nephrotic syndrome. The renal biopsy revealed a FSGS not otherwise specified. He was successfully treated symptomatically. One and a half years later, and without treatment for 1 year, he is still in hematologic remission, with a remaining renal insufficiency. CONCLUSIONS Our patient had a particularly long response to belamaf mafodotin of more than 2.5 years, which is still ongoing. This is particularly remarkable because the very unusual acute renal impairment was not myeloma related. This is a very rare case of FSGS in a myeloma patient, potentially linked to a COVID-19 infection considering the chronology of the events and the immunosuppressive status secondary to the malignancy and its treatment.