Background: Management of unusual not scar ectopic pregnancies (UNSEPs) is an unexplored clinical field because of their low incidence and lack of guidelines. Objective: To report the clinical presentation, the first- and second-line treatment and outcomes of UNSEPs. Methods: We retrospectively collected patients treated for UNSEP (namely cervical, interstitial, ovarian, angular, abdominal, cornual and intramural), their baseline characteristics, risk factors, symptoms, diagnostic pathway and the type of first-line treatment (medical, surgical or combined). We further collected treatment failures and the type of second- line treatment. We assessed treatment outcomes, time to serum beta human chorionic gonadotropin (β-hCG) level negativity, length of recovery, follow up and return to a normal menstrual cycle. Results: From 2009 to 2019, we collected 79 cases. Of them, 27 (34%), 23 (29%), 12 (15%), 8 (10%), 6 (8%) and 3 (4%) were cervical, interstitial, ovarian, angular, abdominal and cornual, respectively. Forty women (50.6%) were submitted to medical treatment, mostly methotrexate based; conversely, 36 patients (45.6%) underwent surgery and only 3 women (3.8%) received a combined treatment. The success of first-line treatment rate, regardless of UNSEP location, was 53% and 89% for medical and surgical treatment, respectively. Treatment failures (21 patients) were submitted to second-line treatment, respectively 47.6% and 52.4% to medical and surgical approach. Of interest, cervical pregnancies achieved the lowest rate of first-line medical treatment success (22%) and received more frequently (69%) a subsequent surgical approach with no hysterectomy. Interstitial pregnancies were submitted to surgery mostly for a matter of urgency (71%), otherwise, they were treated with a medical approach both at first- and second-line treatment. Ovarian pregnancies were treated with ovariectomy in 44% of the cases submitted to surgery. Angular pregnancies underwent surgery more often, while all the abdominal pregnancies underwent endoscopic or open surgery. Cornual pregnancies received cornuostomy in 75% of the cases. Overall, the need for blood transfusion was 23.1% among the patients submitted to surgery. The median length of hospitalisation was shorter for women submitted to surgical first-line treatment (5 vs. 10 days; p = 0.002). In case of first-line medical treatment and in case of failure, we found an increase of 3 days (CI95% 0.6-5.5; p = 0.01) and of 3.6 days (CI95% 0.89-6.30; p = 0.01) in the length of hospitalisation, respectively. Negative β-HCG levels were obtained earlier in the surgical group (median 25 vs. 51 days; p = 0.001), as well as the return to normal menstrual cycle (median 31 vs. 67 days; p < 0.000). Post-treatment follow-up, regardless of the failure of first-line treatment was shorter in the surgical group (median 32 versus 68 days; p= 0.003). Conclusion: Cervical pregnancies were successfully managed with a surgical approach without hysterectomy, and hence, we suggest avoiding medical treatment. No consensus emerged for other UNSEPs. Ovarian, angular and interstitial pregnancies are burdened by a non-conservative approach on the utero-ovarian structures. The surgical approach led to shorter recovery, earlier β-hCG negativity and shorter follow-up, even though there is an increased risk for blood transfusion.