Background: In a developing country, infectious disease remains the most important cause of fever, but the noncommunicable diseases, like malignancy, are fast becoming important differential diagnoses. An important clinical problem is the cases labeled as fever of unknown origin (FUO), which often evade diagnosis. Objective: The present study was undertaken to find the cause of FUO in a tertiary care hospital of eastern India. Materials and Methods: This is a prospective study of inpatients, with regard to both clinical signs and investigations. Results: The main diagnosis in the end was tuberculosis, closely followed by hematological malignancy. A substantial number of cases remained undiagnosed despite all investigations. The provisional diagnosis matched with the final in around two thirds of the cases. While for younger patients leukemia was a significant diagnosis, for older ones, extra-pulmonary tuberculosis was a main concern. Interpretation: In India, infectious disease still remains the most important cause of fever. Thus the initial investigations should always include tests for that purpose in a case of FUO. Conclusion: Geographic variations and local infection profiles should always be considered when investigating a case of FUO. However, some of the cases always elude diagnosis, although the patients may respond to empirical therapy.