Methotrexate (MTX) is an effective, economical and safe drug used in the treatment of ectopic pregnancy. Complications are very rare. Herein, we reported a case of febrile neutropenia following single low-dose methotrexate for the treatment of ectopic pregnancy. Febrile neutropenia developed on day 4 of single-dose methotrexate administered intramuscularly. Although methotrexate single-dose regimen is quite effective and safe in ectopic pregnancy, febrile neutropenia can occur very rarely.