Ectopic pregnancy is an urgent clinical condition that represents a serious hazard to reproductive power, and thus threatens woman's health. Commonly, methotrexate is considered for early resolution of placental tissue. Despite its potential advantages such as minimizing hospitalization and quick recovery, its high skin and gastrointestinal side-effects and requiring time monitoring may limit its application. Recently, high effectiveness of the single-agent chemotherapy agents, such as Actinomycin D, has been suggested. Herein, a case of methotrexate-resistant EP that was successfully treated with Actinomycin D was described.