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Abstract Background Immune reconstitution inflammatory syndrome (IRIS) is a constellation of inflammatory disorders that are unmasked after the initiation of anti-retroviral therapy (ART) in Human immunodeficiency virus (HIV) infected patients. Unmasking lymphoma IRIS is a relatively rare manifestation after initiation of anti-retroviral therapy. Case presentation We report a 44-year-old male with HIV on 4 months of ART presenting with pyrexia of unknown origin with a diagnosis of unmasking Hodgkin’s lymphoma IRIS stage IV with B symptoms. This case portrays the importance of recognizing the possibility of Hodgkin’s lymphoma as a possible manifestation of IRIS within the first 6 months of initiation of ART. Conclusion Patients presenting with pyrexia of unknown origin and lymphadenopathy within the first 6 months of initiation of ART, lymphoma diagnosis should be on the high threshold of suspicion as portrayed by our case.