A 30-year-old woman with severe active left sided Ulcerative Colitis (UC) (Montreal classification E2, Mayo endoscopic subscore 3 at the last colonoscopy), who had already failed multiple courses of steroids and 5ASA, was referred to our third level Gastroenterology Unit because of rapid worsening of rectal bleeding and dyspnea of 4 days duration. Chest X-rays showed a round lesion in inferior right lung lobe (Fig. 1). In the internal side of the left popliteal region the patient had a purple skin lesion (diameter 5 cm), compatible with Pyoderama Gangrenosum (PG) (Fig. 2). Blood tests showed: WBC count 17.160/mmc, Hb 9.9 gr/dL, C Reactive Protein - CRP - 6.37 mg/dL, AST/ALT 54/158 U/L. Stool cultures were negative, such as screening for hepatotropic viruses (HAV, HBV, HCV, EBV) and for autoimmune diseases (ANA, AMA, SMA, LKM). We started antibiotic therapy with ciprofloxacin 200 mg bid and metronidazole 500 mg qd iv (prolonged for 14 days), and topical tacrolimus bid for the treatment of PG. Before starting steroid therapy we performed a High-Resolution CT, confirming a nonhomogeneous 2.5 cm diameter lesion, close to the pleura, with irregular borders compatible with a benign lesion (Fig. 3). Blood cultures and fungal antigens screening were negative; serum IgM for CMV and plasma CMV-DNA were positive. We suspected hence a CMV-related pneumonia, causing at the same time the hepatitis and the UC recrudescence. Ganciclovir was administered for 21 days obtaining negative viremia; we finally started steroid therapy with prednisone 50 mg per os once daily, with nevertheless a poor improvement of intestinal symptoms. A CT chest scan performed 2 months later showed a dimensional growth of the lung lesion (until 3 cm diameter) and patient underwent a bronchoscopy with broncho-alveolar lavage (BAL), which confirmed chronic inflammatory cells infiltrate; acid-fast stain, culture, and PCR for tuberculosis were negative, as well as molecular test for CMV. A CT-guided biopsy was therefore performed and histology showed lymphocytes, granulocyte, and activated mesothelium, whereas immunochemistry for Anti-keratin antobodies (AKA) was negative: these findings were consistent with pulmonary non-necrotizing granuloma (Fig. 4). Even if the patient had not renal or nasopharyngeal involvement, we performed a cANCA screening (negative), excluding a Wegener's Granulomatosis. Because of a further worsening in clinical condition, we started a "rescue therapy" with cyclosporine 4 mg/kg iv combined with azathioprine (AZA) 2.5 mg/kg/day for maintenance. After a great improvement in the first 72 h, the patient reported rapid onset of nausea and vomiting and a moderate recurrence of UC (3-5 bloody stools emissions, abdominal pain). AZA was therefore discontinued for intolerance. Giving the presence of the refractory UC, the decision to perform a restorative total colectomy with temporary protective ileostomy and delayed proctectomy was taken. A rectoscopy after few weeks showed the persistence of severe inflammation in the rectal stump. We attempted a treatment with infliximab (IFX), 5 mg/kg at week 0, week 2, and week 6, observing only a partial improvement in intestinal disease; the patient, moreover, manifested a severe allergic reaction, accompanied by a progressive worsening of PG, and IFX was then discontinued. Proctectomy with ileal pouch-anal anastomosis (IPAA) was then performed. Postoperative course was regular, PG achieved the remission in few weeks after the complete removal of the rectum (Fig. 5) and subsequent chest CT scan showed the concomitant resolution of the pulmonary lesion (Fig. 6).