Mixed connective tissue disease (MCTD), a multisystem autoimmune disease that was first proposed in 1972, has overlapping features with other autoimmune diseases. In recent studies, mixed connective tissue disease has been reported to change into other connective tissue diseases (CTD; such as systemic lupus erythematosus [SLE], polymyositis, and systemic sclerosis [SSc]) in the long term. We report the case of a 58-year-old Japanese man diagnosed with mixed connective tissue disease 15 years ago. During his clinical course, he developed discoid lupus erythematosus, pancytopenia, a low complement titer, proteinuria, and hematuria. He also turned positive for the anti-double-stranded deoxyribonucleic acid (dsDNA) antibody. A kidney biopsy revealed lupus nephritis (LN) class IV. Therefore, we considered this to be a shift from mixed connective tissue disease to systemic lupus erythematosus. We changed his treatment to lupus nephritis, after which he remained in remission. Our case suggests that mixed connective tissue disease may shift to other connective tissue diseases over a long period; therefore, it is necessary to identify whether patients with mixed connective tissue disease fulfill the diagnostic criteria for other connective tissue diseases when new manifestations appear.