Systemic lupus erythematosus (SLE) is a connective tissue disease of unknown etiology that predominantly affects women of childbearing age. We report a case of male systemic lupus erythematous with antinuclear antibodies and typical clinical presentations of multiple skin lesions, polyarticular joint pain, fatigue, anorexia, and hair loss. Full evaluations were used to establish a diagnosis of SLE. The lower prevalence of SLE among males and antinuclear antibody-negative patients poses a great challenge for diagnosis. Therefore, as primary care doctors, we need to have a high suspicion of systemic lupus erythematous even in male and antinuclear antibody-negative patients. Thus, early treatment may help patients improve their quality of life.