Patients with Ro/SSA autoantibodies can develop cutaneous lupus erythematosus and photosensitivity. The aim of this study was to evaluate disease progression and clinical outcome in Ro/SSA-positive patients after 2 years in a prospectively followed cohort. A total of 102 previously clinically and serologically characterized Ro/SSA-positive patients received a questionnaire 2 years after the baseline investigation. Evaluation of 98 questionnaire responses was performed and clinical examination was offered to patients with cutaneous lupus erythematosus established at baseline, or skin symptoms developed over the 2 year period since baseline. Skin symptoms (42%) and arthralgia (31%) were common self-reported health-related answers. Twenty of the 98 patients (20%) showed disease progression with development of new diagnoses such as drug-induced subacute cutaneous lupus erythematosus. This prospective study reveals that new autoimmune diseases and skin disease progress are common in Ro/SSA-positive patients also in the short-term perspective, and stresses the importance of regular follow-up of these patients.