Infective endocarditis (IE) is an inflammatory disease involving a proliferative-destructive processes, usually of streptococcal or staphylococcal etiology. It may also be caused by the physiological flora of the oral cavity, mainly gram-negative bacteria from the HACEK group. IE typically develops in damaged areas of the endocardium. Bacterial vegetations are found in majority on valves but they may be as well visualised in blood vessels, ventricles, on mechanical valves, electrodes and intracardiac catheters. Risk factors for endocarditis concern the growing population of adults with congenital heart disease and patients with frequent healthcare contact for other comorbidities, also patients who are immunocompromised, treated with hemodialysis or use intravenous drugs. The diagnosis of IE is made by the use of transthoracic or transesophageal echocardiography, also other imaging techniques are used. Blood cultures also should be taken. However, it was estimated that approximately 10% of patients have cultures and serologic tests negative for IE. In our study we present a case of a 51-year-old man with end-stage renal disease treated with peritoneal dialysis for 3 weeks prior to hospital admission with an acute infection of unknown origin. Infective endocarditis was suspected based on echocardiography examination. In this case PET-CT (positron emission tomography/computed tomography) was performed for verification. Its result as well as sterile blood cultures did not fully confirm the diagnosis of IE. Despite the access to highly specialized diagnostic methods and broad spectrum antibiotics the diagnosis and treatment were not easy. This story of patient’s disease can be the confirmation that IE is heterogeneous in etiology, clinical manifestations, and course.