OBJECTIVE It has been shown that application of molecular biological techniques to surgical margins of some cancers could predict risk of local recurrence. However, the optimal length of surgical resection with tumor-free surgical margins for esophageal squamous cell carcinoma (ESCC) is unknown. This study was conducted to evaluate the optimal length of surgical resection for ESCC with molecularly tumor-free surgical margins marked by p53 and Ki67.METHODS Surgical specimens from 70 patients with ESCC were collected for study. The lengths of the upper margin, tumor, and lower margin of every specimen were measured during the operation. Each specimen was divided into three large pathologic sections, stained with H&E and immunohistochemically for p53 and Ki67, and examined microscopically.The lengths of the upper and lower resection ends were measured for p53 and Ki67 positive expression. The actual surgical lengths were calculated by the principle of rational shrinkage.RESULTS All surgical margins were histologically tumor-free, while the positive rates of p53 and Ki67 were 66% and 54%. The positive rates of p53 and Ki67 in the upper resection end were 17% and 20%. The mean lengths of the upper resection end showing p53 and Ki67 positive expression were 1.08 ±1.12 cm and 1.64 ±1.01 cm, and the maximum lengths were 3.73 cm and 3.26 cm. The positiver ates of p53 and Ki67 in the lower resection end were 20% and 23%. The mean lengths of the lower resection end of p53 and Ki67 with positive expression were 1 .11±1.15 cm and 1.34±0.94 cm, and the maximum lengths were 3.73 cm and 3.61 cm.CONCLUSION The optimal length of surgical resection with molecularly tumor-free surgical margins of ESCC is not more than 5 cm.