Objectives <p>This study aims to propose a novel ultrasound classification for tubal ectopic pregnancy (TEP) and explore relationships between sonographic features and serum markers.</p> Materials and methods <p>A retrospective single-center cohort study was conducted involving TEP patients, who were classified into two groups (simple gestational sac (GS)-like and complicated masses) based on ultrasound characteristics indicating a clear trophoblastic ring, hematosalpinx, or clear salpinx structure. Statistical comparisons and Spearman’s rank correlation analyses were performed.</p> Results <p>In this study, 320 women with TEP were classified into a simple GS-like mass group (<i>n</i> = 128) and a complicated mass group (<i>n</i> = 192). Compared with complicated masses, simple GS-like masses were smaller, had higher β-human chorionic gonadotropin (β-hCG) levels, and higher color Doppler flow imaging grades (all <i>p</i> &lt; 0.05). β-hCG was strongly correlated with mass size in simple GS-like mass cases (<i>r</i> = 0.720, <i>p</i> &lt; 0.01), but weakly correlated in complicated mass cases (<i>r</i> = 0.211, <i>p</i> &lt; 0.01). Hemoglobin levels were inversely correlated with pelvic free fluid depth in complicated masses (<i>r</i> = −0.344, <i>p</i> &lt; 0.01).</p> Conclusions <p>The proposed ultrasound classification differentiates TEPs into subtypes with unique clinical and pathophysiological profiles. The variation in the correlation among sonographic indices and serum markers across TEP subtypes underscores the necessity for tailored clinical strategies. In simple GS-like masses, β-hCG and mass size are positively correlated, thus, clinical decisions could be made based on these two factors as recommended by guidelines. However, in complicated masses, β-hCG and mass size were poorly correlated, thus, the mass size should be deemphasized. Decisions should be made through comprehensive assessments under such circumstances.</p> Critical relevance statement <p>The novel ultrasound-based classification proposed in this study differentiates tubal ectopic pregnancies into simple gestational-sac-like and complicated subtypes presenting with different correlations between sonographic indices and serum markers, which require tailored strategies in clinical settings.</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Addresses the lack of unified ultrasound classification for TEP.</p> </ItemContent> <ItemContent> <p>Different TEP types reveal distinct sonographic and serum profiles, with various relationships between them.</p> </ItemContent> <ItemContent> <p>This novel classification aids in tailored treatment and clinical decision-making.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>