Systemic lupus erythematosus (SLE) is a systemic disease that affects several organs. The diagnosis was performed using the international classification criteria updated in 2019. The significance of antinuclear antibodies (ANAs) with a centromere pattern has not been clearly documented in these criteria. We herein report a patient with ANAs with a centromere pattern and anti-centromere antibodies, without anti-Sm antibodies or anti-dsDNA antibodies, who developed severe lupus nephritis, neuropsychiatric SLE, and lupus pleuritis. The patient was successfully treated with prednisolone, hydroxychloroquine, mycophenolate mofetil, cyclophosphamide, and belimumab, despite several relapses. Anti-centromere antibodies are not regarded as characteristics of SLE but can be detected in SLE patients with severe organ involvement.