Interstitial pregnancy is defined as the presence of a gestational sac in the most proximal section of the fallopian tube. Management of interstitial pregnancy remains a debated topic. Depending on hemodynamic stability, size of pregnancy, depth of surrounding myometrium, and desires for future fertility, interstitial pregnancy can be managed medically or surgically. We reviewed the literature in December 2020 using keywords “interstitial pregnancy”, “medical treatment”, “methotrexate”, and “mifepristone”. Articles published from January 1991 until 2020 were obtained from databases EMBASE, SCOPUS, and PUBMED. We describe the case of a patient with an interstitial pregnancy that was managed with a total medical approach in August 2020 at Burlo Garofolo Hospital. The patient was asymptomatic and hemodynamically stable, with a high level of serum β-hCG (22,272 mUi/mL). We used the combination of methotrexate (MTX) and mifepristone. Medical therapy was effective leading to interstitial pregnancy resolution in 51 days without collateral effects for the patient. We found seven previous cases reported in the literature. Our purpose is to underline the efficacy of medical therapy with systemic multidose MTX associated with a single oral dose of mifepristone and also folinic acid when is present a viable fetus and a high serum β-hCG level.