Mimecan mRNA was present in a limited number of mouse and human tissues, however, abundant mimecan mRNA was observed in the lung tissue. Therefore, we hypothesize that mimecan could serve as a biomarker for differentiating various histological types of lung cancers. In humans, the mimecan mRNA was found most abundant in ovary and less abundant in lung by using Northern blot analysis. Moreover, the mimecan was expressed strongly in the epithelial cells of the bronchial wall and weaker in the epithelial cells of the alveolar sacs by in situ hybridization and immunohistochemical analysis. Furthermore, the mimecan immunoreactivity was found in 103 (97.2%) of 106 non-small cell lung cancers (NSCLCs). Nevertheless, a large majority of small cell lung cancers (SCLCs) (50/56, 89.3%) showed negative immunoreactivity to mimecan polyclonal antibody. A significant difference of mimecan immunoreactivity was found between NSCLC and SCLC (P<0.00001). This is the first study showing that mimecan could serve as an excellent pathological biomarker to distinguish NSCLCs from SCLCs.