Background <p>Esophageal cancer (EC), especially esophageal squamous cell carcinoma (ESCC) in China, is a major cause of cancer-related mortality. While lymph node (LN) dissection is crucial for staging and prognosis in early-stage EC, the optimal extent of dissection based on tumor location remains undefined. This study aimed to establish location-specific LN dissection thresholds to improve outcomes in clinical T1-2N0M0 ESCC.</p> Methods <p>We conducted a retrospective analysis of 1017 patients who underwent esophagectomy at two Chinese cancer centers between March 2015 and December 2018, with follow-up until December 2023. LNs were categorized into upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd) compartments. Optimal cut-off values for total and regional LN counts were determined using Maximally Selected Rank Statistics. Overall survival was analyzed using Kaplan–Meier methods, and independent prognostic factors were identified using Cox regression.</p> Results <p>Dissection of ≥ 17 total LNs, including at least one LM LN and 14 Abd LNs, was associated with significantly improved survival. Location-specific recommendations were upper thoracic tumors, ≥ 19 total LNs (≥ 5 UM, ≥ 14 Abd); middle thoracic tumors, ≥ 17 total LNs (≥ 1 LM, ≥ 6 Abd); lower thoracic tumors, ≥ 18 total LNs (≥ 9 UM, ≥ 1 LM). Multivariate Cox regression identified total and LM LNs as independent prognostic factors for overall survival in the entire cohort, total RLNs in the upper thoracic subgroup, and LM RLNs in the middle thoracic subgroup.</p> Conclusions <p>These findings define location-specific LN dissection thresholds that may improve survival outcomes in clinical T1-2N0M0 ESCC. These data provide surgeons with evidence-based guidance for tailoring LN dissection strategies based on tumor location.</p>