Background. Secondary hemophagocytic syndrome (SHPS) is a reaction of systemic hyperinflammation triggered by infectious, tumor, or autoimmune processes. With no immunosuppressive (modulating) therapy most patients die from multiple organ failure. Aim. To describe organ lesions characteristic of SHPS patients. Materials & Methods. The retrospective study included patients treated from June 2009 to June 2019. SHPS was diagnosed using HLH-2004 criteria and H-Score. The analysis focused on the incidence and character of lesions in lungs, central nervous system, liver, skin, and cardiovascular system. All patients with persistent fever received anti-infective treatment with broad-spectrum antibiotics in line with local hospital practice. Patients with collagenosis and tumors, which caused SHPS, received standard immunosuppressive and antitumor therapy, respectively. Results. The analysis covered the data of 91 patients (41 man and 50 women), median age was 58 years (range 2–90 years). SHPS was caused by hematological malignancies (n = 52; 57 %), infections (n = 11; 12 %), autoimmune diseases (n = 5; 6 %), and allogeneic hematopoietic stem cell transplantation (n = 13; 14 %). In 10 (11 %) patients no cause was identified. Immunosuppressive therapy was administered to 71 (78 %) patients. Overall survival was 27 % (median 15 days) with median follow-up for alive of 540 days (range from 7 days to 10 years). Clinically significant organ lesions were identified in 76 (83 %) patients. Most commonly SHPS was reported together with polyserositis, respiratory and hepatic disorders, and neurological symptoms from focal deficit to seizure status. Less often skin lesions (from macular rash to epidermolysis bullosa) and such cardiovascular disorders as arrhythmia and/or arterial hypotension were observed. The effective SHPS therapy resulted in restoration of organ functions. Conclusion. SHPS can cause respiratory disorders, polyserositis, different neurological disorders, cytopenia in patients with unexplained fever and cytolytic and/or cholestatic syndrome. Primary organ lesions as well as clinical and laboratory manifestations of SHPS may vary in different patients.