Abstract: Objective:To investigate the correlation of neuroendocrine (NE) differentiation in lung adenocarcinoma with its biological behavior and prognosis. Methods:We reviewed the paraffin-embedded specimens and clinical materials of 86 lung adenocarcinoma cases ( 45males and 61females) seen in our hospital between June 2005 and December 2006. These cases were followed up for3 years, and none of them underwent radiation or chemotherapy. Immunohistochemical EnVision two-step method was uded to detect the expression of NSE, CgA and Syn proteins. The data were analyzed with SPSS statistics software. Kaplan-Meier survival curve and Log-rank test were constructed. Results: Of the 86patients with lung adenocarcinoma, 35cases had NE differentiation simultaneously (40.7%). The statistical analysis showed a significant association between lung adenocarcinoma with NE differentiation and cancer recurrence and histological differentiation. In addition, the positive rate of CgA, NSE and Syn in lung adenocarcinoma was 27.9%,50.0%, and43.0%, respectively. The expression of Syn was correlated with pathological type, histological differentiation, lymph node metastasis, postoperative recurrence and 3-year survival rate ( P=0.001 ). Conclusion:NE differentiation may be an potential metastatic indicator for bi-ological behavior of lung adenocarcinoma. Combined detection of NSE and Syn markers is recommended to detect NE dif-ferentiation in lung adenocarcinoma. Positive expression of Syn indicates poor prognosis.