In the diagnostic of systemic sclerosis (SSc), both anti-centromere (ACA) and anti-topoisomerase I (ATA) antibodies are considered mutually exclusive, though their coexistence has been also reported in some patients. Notably, nintedanib has been approved for the treatment of interstitial lung disease associated to SSc. Herein, we present the clinical case of a 41-year-old woman with SSc who shows an immunological seroconversion (from ACA positivity to a coexistence of ACA and ATA antibodies) together with changes in her clinical phenotype. Besides, the patient responds positively to the treatment of her lung involvement with a combination of immunomodulators and antifibrotic agents.