OBJECTIVE: The aim of this study was to assess the prognostic value of serum carboxyterminal telopeptide of type I collagen (ICTP) in ovarian cancer. Serum CA125 was used as a reference marker. METHODS: Forty-five patients with epithelial ovarian cancer were monitored with serial measurements of serum concentrations of ICTP, a degradation product of type I collagen likely to come about via the matrix metalloproteinase pathway. RESULTS: The patients with a good prognosis had significantly lower serum ICTP concentrations than the patients with a poor prognosis both before the operation and at all the postoperative time points studied (3, 6, 9, 12, 18, and 24 months), whereas a corresponding difference in CA125 was first seen after a 12-month follow-up. In multivariate regression analysis, the 9-month serum ICTP concentration remained the only independent prognostic indicator of all biochemical, clinical, and histological variables. The postoperative serum ICTP concentration did not correlate with the clinical stage, the grade of differentiation, or the presence of residual tumor. In contrast to ICTP, postoperative serum CA125 correlated with the clinical stage and the presence of residual tumor. CONCLUSIONS: Because our ICTP test does not detect defectively cross-linked carboxyterminal telopeptides of type I collagen, which is the predominant form in malignant ovarian tissue, the excess ICTP of ovarian cancer patients must originate from the tissue around the tumor, where the malignancy is causing tissue damage. As an indicator of invasion, the serum ICTP test opens up new possibilities to assess the clinical behavior of ovarian cancer and, in the future, also the effect of possible antiproteinase treatment in ovarian cancer.