Cysteine-rich protein 61 (Cyr61) is a member of a family of growth factor-inducible, immediate-early genes. In this report, the authors measured the expression of Cyr61 mRNA in 94 human lung tumors and their normal matched lung samples. The Cyr61 mRNA levels were quantified by real time reverse transcriptase-polymerase chain reaction and calculated as a tumor/normal Cyr61 mRNA ratio in each case. Compared with normal matched lung tissues, expression of Cyr61 was decreased in 74 of 94 (79 percent) lung tumors. Differences in distribution of patient characteristics, such as gender, age, tumor size, and pathological diagnosis, between high or low Cyr61 expressing groups were not statistically significant. However, differences in distribution of clinical stage between high or low Cyr61 expressing groups was statistically significant; that is, the Cyr61 low expressor group was clinically more advanced than the Cyr61 high expressor group (p = 0.046). Furthermore, Cyr61 levels of the patients with N0 and N1 diseases were significantly higher than the expression in the N2 patients (p = 0.047). The 3-year survival between the Cyr61 very low tumor expressor group compared to matched normal lung (39 patients) and the higher Cyr61 expressor group (52 patients) was statistically significant (59 versus 91 percent; p = 0.05). Taken together, Cyr61 appears to guard against metastatic disease because low expression is associated with more advanced disease; and therefore, expression levels of Cyr61 correlate with the prognosis of lung cancer.