A 29-year-old man was admitted because of fever, arthralgia and swelling of the cervical lymph nodes. A diagnosis of histiocytic necrotizing lymphadenitis (HNL) was made based on the findings of a lymph node biopsy. At first, piperacillin sodium (PIPC) was started, but a spiking fever persisted. We therefore changed the PIPC treatment to minocycline. On the following day, his clinical and laboratory findings were dramatically improved. After administering minocycline for 10 days, the HNL symptoms completely disappeared. He has been in good health for 3 years since undergoing treatment. This case strongly indicates that minocycline-sensitive microorganism(s) may be related, at least in part, to the etiology of HNL.