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Objective : Given the great variability of human chorionic gonadotropin (HCG) levels after a single dose of methotrexate (MTX) for ectopic pregnancy, it remains complicated to identify cases undergoing persistence until a week from treatment. We evaluated whether pre-treatment patterns of HCG levels could be useful for an earlier detection of persistent trophoblast. Study design : A retrospective study on 62 patients treated by a systemic single dose of methotrexate (50 mg/m 2 ) for an ectopic pregnancy. Samples for HCG detection were obtained on days −2 and 0 before the therapy, on days +3, +7 and then weekly until values were undetectable. Patients were divided into three groups: Group U (up, meaning “increasing”) and Group D (down, meaning “decreasing”) when HCG levels on day 0 were respectively higher or lower than day −2 level of more than 20% and Group P (plateau) when the difference between day −2 HCG level and the level on day 0 was less than 20%. Results : All the patients of Group D underwent a complete resolution, with a percentage of 33.3% of cases who underwent an initial rise of HCG levels on day +3. The percentage of cases undergoing an initial rise of HCG levels in Group U patients was significantly higher than in Group P patients (60.0% versus 28.6%), but the resolution rate resulted similar in the two groups. For patients of Group P , an increase of HCG levels on day +3 was significantly correlated to the failure of the therapy. Indeed, comparing the cases with an immediate increase of HCG levels to the cases with immediate decrease of HCG levels on day +3, the persistence rate was 80% for the former and 12% for the latter ( P Conclusion : An initial rise of HCG levels after the therapy does not seem to have a clinical relevance in Group D and Group U patients, it well correlates to trophoblastic persistence in Group P patients.