Aim: Pyoderma Gangrenosum (PG) is a neutrophilic dermatosis that represents a clinical challenge because of the frequent recurrence of the disease. The aim of our work was to evaluate the use of Baricitinib, an oral JAK1/2 inhibitor, as a third-line biologic agent for the treatment of a multi-refractory PG case. Method: A 70-year old woman was admitted to our clinic in February 2022 with right foot lesions diagnosed as PG. The patient was affected by chronic lymphoid leukemia in remission and was unsuccessfully treated with Guselkumab, Adalimumab and cyclophosphamide. Because of the absence of clinical improvement, Baricitinib 8 mg/day and Prednisone 25 mg/die were started (T0). Proper local wound management was carried out and at T7 we performed an homologous graft. At each visit, Wound Bed Score (WBS) was assessed and pain was evaluated with Numerical Rating Scale (NRS). Results / Discussion: At T0 the Wound Bed Score (WBS) was 8, while pain measured through the Numerical Rating Scale (NRS) was assessed at 9. At T7 there was an improvement of pain and a similar wound severity (WBS 8; NRS pain 6), while at T21 pain was further reduced (NRS pain 5) and no signs of clinical worsening appeared at the graft site. Conclusion: In clinical cases of multi refractory PG, homologous graft combined with Baricitinib and Prednisone therapy could represent a further therapeutic choice which, in our short experience, allows better management of local pain and determines an arrest of the inflammatory component.