Background and study aim: Fever of unknown origin (FUO) constitutes one of the greatest challenges of clinical practice. It's defined as fever more than three weeks with fever above 38.3ºC on several occasions which remains undiagnosed after 3 days of investigations in the hospital or after three outpatient visits. Measurement of ferritin in serum is unfortunately an underutilized diagnostic test in patients with FUO. Highly elevated serum ferritin levels in patients with FUO should prompt further testing to arrive at a specific diagnosis.The aim of this study is to verify the role of serum ferritin levels in differentiation between fever of  unknown origin (FUO) caused by infectious and noninfectious diseases. Patients and methods: This study included 40 patients with FUO were hospitalized at Menouf Fever Hospital between July 2013 and June 2014, and 20 volunteers of matched age and gender as a control group. According to the final diagnoses, four causes were identified, including infectious diseases, malignant diseases, collagen diseases and miscellaneous diseases. Laboratory tests, radiological examination and invasive procedures as bone marrow biopsy and lymph node biopsy were done according to cases. Serum ferritin was measured by Human Ferritin ELISA Kit. Results: Of the 40 patients, 20 were caused by infectious diseases, 10 were caused by malignant diseases, 7 were caused by collagen diseases and 3 by miscellaneous diseases (two cases of FMF and one case of drug fever). Serum ferritin levels in infectious diseases was lower than that in noninfectious diseases,where it was 457.6 ng/mL (±248.01) for the  infectious disease group and1241.5ng/mL (±1163.80) forthe noninfectious diseases group. Statistically significant difference was found between the two groups (p<0.05). Conclusion: An optimal cutoff value of serum ferritin level >555 ng/mL can predict FUO caused by a noninfectious disease.