A 50-year-old patient presented with hematuria and a mass in the posterior wall of the bladder discovered with an ultrasound scan. He had already been hospitalized months earlier for an ischemic stroke treated with fondaparinux and clopidogrel for a month. Following an episode of melena, he underwent blood transfusions and performed a gastroduodenoscopy, with clinical diagnosis of erosive gastritis with a discrete eosinophilic infiltrate. The anamnesis was negative for allergies, asthma, or respiratory diseases. Physical examination revealed dark macules alongside the interdigital space of his hands. After a cystoscopy, which confirmed the ultrasound finding, he underwent an endoscopic resection of the lesion with a histological report of polypoid cystitis. Blood transfusions and hemostatic transurethral resection (TUR) surgery were performed due to incoercible hematuria and consequent anaemia. In the following, he was readmitted to the Emregency Room (ER) and underwent further blood transfusions and hemostatic TUR with new biopsy sampling. Cystoscopy showed inflammation of the mucosa and an ulcerated pseudopolypoid lesion on the bottom of the bladder (Fig. 1). The histological examination (Fig. 2) revealed a rich eosinophilic-giant cell lympho-granulocyte infiltrate with granulomatous aspects and some necrotic focus, in the absence of peripheral hypereosinophilia. The patient returned to the hospital for hematuria after about one week and underwent blood transfusions and hemostatic TUR with biopsy sampling again. The histological examination showed intense chronic inflammation with a large amount of eosinophilic granulocytes, in the absence of microorganisms. Uro-computerized tomography (CT) was performed and the results showed a diffuse thickening of bladder walls, with low capacity and small lumen, enlarged regional and para-aortic lymph nodes. Microbiological testing (Quantiferon, Mycobacterium tuberculosis in urine, and Schistosoma eggs in stool) were performed, all with negative results. As hematologists suggested, the study of coagulation factors and thromboelastogram (TEG) was performed in the suspicion of a hemostasis disease, but with a negative result.Due to gross hematuria, another hemostatic TUR and blood transfusions were performed. The biopsy samples were sent for microbial analysis for the search of parasites, fungi, and bacteria. The result was positivite for Klebsiella pneumoniae and Enterococcus faecalis on histological specimens. The infection was treated with fosfomycin (4 g/thrice a day) and vancomycin (1 g/twice a day). It was decided to avoid radical cystectomy in the young patient. Rheumatological and neurological counseling were required: the rheumatologic etiology was neglected, but antinuclear antibodies (ANA) were found with fine-speckled pattern positivity (1:320); the neurological examination revealed polyneuropathy of upper and lower limbs. After finding total IgE 11 times higher than the cut-off, therapy with Cetirizine (10 mg/die) was set and hyperbaric therapy (2 h/day for 5 days) was performed. Positive urine culture confirmed the infection on the histological finding; therefore, cortisone therapy was postponed. He was discharged with a bladder catheter, cetirizine (10 mg/day), and prednisone (30 mg/day) therapy, in order to keep the disease inactive. The macules and gross hematuria disappeared and polyneuropathy improved, but gross hematuria reappeared with new fondaparinux therapy for orthopedic injury. Triphasic contrast CT highlighted flogosis of the maxillary sinuses and low-capacity urinary bladder with thickening of the posterolateral wall and an effusion nearby the resection area (Fig. 3). Hematochemical analysis showed iron-deficiency anemia and total IgE 3 times higher than the upper limit. An urinary bladder biopsy revealed a rich eosinophilic and lympho-monocytic infiltrate without perivascular fibrinoid necrosis. Rheumatologic counseling excluded vasculitis and hematological counseling suggested to perform a bone marrow biopsy (BMB), which revealed a hypereosinophilic crisis. In addition, research for FIP1L1-PDGFR1alpha fusion gene was prescribed. Corticosteroid and antihistaminic therapy was set and hematuria resolved. If symptoms reappear, cystoscopy will be performed and second line therapy will be considered.