Recent studies point out that cytokeratins (CKs) are involved in dynamic cell remodeling during cancer progression and particularly, CK expression patterns have been associated with invasion and metastasis. In oesophageal squamous cell cancer (ESCC), lymph node (LNN) metastasis is an important step in disease progression, invariably associated with an ominous prognosis. To assess whether specific CK expression patterns could represent reliable markers of tumor progression, a series of 111 ESCCs (59 lymph node-positive, 52-negative) derived from the high- incidence area of Linxian (Northern China), were subjected to immunohistochemical (IHC) analysis with an extensive panel of CK antibodies. Statistically significant differences were observed for CK18 (p=0.01), CK19 (p=0.04) and PKK1 (p=0.02) expression between the LNN-negative and LNN-positive ESCCs. Furthermore, significant correlation between specific CK distribution pattern and progressive disease (i.e., LNN metastasis) was evidenced. The results suggest that CK8, CK18 and CK19 expression and distribution pattern could be of predictive value as a marker of disease progression as defined by the appearance of lymph node metastases in oesophageal squamous cell cancer.