BACKGROUND YKL-40, a member of family 18 glycosyl hydrolases, is secreted by cancer cells. The function of YKL-40 in cancer diseases is unknown, but it is a growth factor of connective tissue cells and probably has a role in inflammation and remodeling of the extracellular matrix, a process also involved in metastatic malignant diseases. High serum YKL-40 has been associated with poor prognosis for patients with colorectal and recurrent breast cancer. AIM OF THE STUDY The purpose of the present study was to examine the prognostic value of plasma YKL-40 in patients presenting with recurring ovarian cancer. METHODS YKL-40 was determined by ELISA in plasma samples from 73 patients with relapse of ovarian cancer shortly before start of second-line chemotherapy. The endpoint used was death because of ovarian cancer. RESULTS Plasma YKL-40 was increased in ovarian cancer patients (median 94 micro g/L, range 20-1970 micro g/L) compared with age-matched controls (33 micro g/L, range 20-130 micro g/L) (p < 0.001). Fifty-five per cent of the patients had a plasma YKL-40 level above the upper normal 95th percentile of controls. Patients with high plasma YKL-40 (i.e. > 130 micro g/L or > 160 micro g/L) at the time of relapse had significantly shorter survival than patients with normal levels (respectively p = 0.007 and p = 0.004). Plasma YKL-40 proved to be an independent prognostic factor in a multivariate Cox analysis (YKL-40 > 160 micro g/L; HR = 2.27) (p = 0.006), including serum CA-125 and clinical/histological parameters. CONCLUSION High plasma YKL-40 is related to short survival in patients with recurrent ovarian cancer.