YKL-40 is a recently discovered glycoprotein which is related in amino acid sequence to the chitinase protein family, but has no chitinase activity. Although the function of YKL-40 is presently unknown, the pattern of its expression by some tissues suggests that YKL-40 could function in tissue remodelling. The diagnostic features and relation to survival of serum YKL-40 have not been examined previously in human malignancies. In the present study YKL-40 was measured in serum obtained from 60 patients at the time that breast cancer recurrence was suspected. The median serum YKL-40 in patients with visceral or bone metastases was 328 and 157 micrograms/l, respectively and significantly higher compared to controls (99 micrograms/l, P < 0.001). Kaplan-Meier survival curves demonstrated that survival rates after 18 months were 24% for patients with high serum YKL-40 (> 207 micrograms/l = the 95 percentile of controls) and 60% for patients with normal serum YKL-40. The significance of the difference between the shorter survival of patients with high serum YKL-40 and the longer survival of patients with normal serum YKL-40 was high (P < 0.0009). When evaluated with other prognostic factors of survival after recurrence of breast cancer, serum YKL-40 and serum lactate dehydrogenase (LDH) were the most significant independent factors. The results indicate that determination of serum YKL-40 can be used as a prognostic marker related to the extent of disease and survival of patients with recurrence of breast cancer. In addition, the serum YKL-40 level may be of value in the follow-up of patients with breast cancer and in evaluating potential metastatic spread.