Background/aims: We first reported in this study that serum placenta growth factor and carcinoembryonic antigen in combination were useful markers for selecting early-stage colorectal cancer patients. The aim of the present study was to determine whether serum placenta growth factor could provide carcinoembryonic antigen-independent prognostic information on patients undergoing curative surgery. Methods: Serum and tissue samples were collected from 158 patients with colorectal cancer and from 50 controls. Serum and tissue levels of placenta growth factor were measured by enzyme-linked immunosorbent assay. The serum placenta growth factor levels in colorectal cancer patients were compared with those in healthy controls, and we retrospectively assessed the association between serum placenta growth factor levels and clinicopathological findings and survival. Results: Expression of placenta growth factor was significantly higher in colorectal cancer tissues compared with non-tumor tissues. The mean serum placenta growth factor level in patients was significantly higher than that in controls and significantly higher in patients with large tumor, lymph-node involvement and distant metastasis. Conclusions: Elevated serum placenta growth factor levels are significantly associated with colorectal cancer development, lymph or distant invasive phenotypes and survival, especially in stage II or III patients.