A 55-year-old man was sent to the ED of our hospital from a Nephrology DH for a relapsing-remitting fever dating to almost a year, associated with exertional dyspnoea during mild efforts. He reported a partial response to antibiotic therapy during the past months. His past medical history included hypertension, an endoscopic prostatic resection for a benign hypertrophy and recurrent pericarditis in the past twenty years; he was also recently admitted to the Internal Medicine service for a likely vasculitis-related acute kidney injury. Physical examination and vital signs were normal, while blood exams showed high creatinine (9.60 mg /dl), anaemia and inflammatory markers elevation. The patient was admitted to the Nephrology service and blood cultures were sent to the laboratory. Due to his history of dyspnoea, he underwent a Cardiology consult and a TTE detected a 11-mm mobile filamentous vegetation on the ventricular side of the non-coronary aortic cusp, with a globally thickened valve and a 12-mm oval mass on the atrial side of the anterior mitral leaflet. Severe aortic and moderate mitral valve regurgitations were also found. Because of the high suspicion of endocarditis a TOE was performed, which confirmed the findings and displayed a mitroaortic junction involvement, with two small abscesses that were perforated both on the ventricular and the atrial side. Blood cultures were positive for multisensitive Streptococcus mutans, the immunological panel highlighted severe hypocomplementemia, positivity for ANA, ANCA and rheumatoid factor; cryoglobulins were also detected together with blood at urinalysis. A CT scan excluded septic embolism and given the high risk of embolization and the local cardiac complications, the patient underwent a double valve replacement with mechanical prosthesis and a ceftriaxone-based antibiotic course is also started. At 4-months follow up the patient is in excellent clinical status and the renal function completely recovered. This case emphasises how endocarditis is a disease with a high impact not only per se, bearing the risk for local cardiac and systemic complications, but also because of the possible immunological burden. Our patient suffered a likely endocarditis-associated cryoglobulinaemic glomerulonephritis (IEAGN), entity known to entail a poor prognosis despite prompt antibiotic therapy. A multidisciplinary management is crucial for the correct management of such complex cases to achieve the best clinical outcome.