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Lenalidomide, an immune-modulatory drug, is used to treat multiple myeloma (MM). Lenalidomide has also been investigated as a treatment for myelofibrosis (MF); however, its efficacy in this setting has not been established. We report a case of secondary MF progressing from polycythemia vera (PV) that had the poor prognostic factor del (7q) and concurrent MM, in which del (7q) disappeared and MF improved after treatment with lenalidomide. A 69-year-old woman presented to our hospital with PV in March 2022. Bone marrow examination revealed grade 2 fibrosis. The diagnosis was secondary MF progressing from PV, with JAK2 V617F and del (7q), along with IgG-κ monoclonal gammopathy of undetermined significance (MGUS). In May 2023, the appearance of new bone lesions indicated progression of MGUS to MM. Treatment with lenalidomide plus dexamethasone achieved a partial response. After this treatment, del (7q) disappeared and MF improved. The efficacy of lenalidomide in MF with del (7q) has never been reported. This case shows that lenalidomide may improve the prognosis of MF with del (7q).