HtrA1 is a serine protease homologue to the bacterial serine-protease HtrA, also known as DegP, a heat shock-induced envelope-associated serine protease. It has been shown that over-expression of HtrA1 in human cancer cells inhibits cell growth and proliferation in vitro and in vivo, thus, suggesting a possible role as a tumor suppressor. The expression of HtrA1 was investigated in depth by means of immunohistochemistry in a large group of human lung cancer specimens and corresponding lymph node metastases. Univariate analysis showed, that the only statistically significant correlation was found between the HtrA1 expression level detected in the primary tumors and in the lymph node metastases. This result was also confirmed when the analysis was restricted only to the cases where both the primary tumor and the autologous lymph node metastasis were available. Our data suggest that HtrA1 may be involved in lung cancer progression by targeting several molecular pathways.