Relationships between serum biomarker levels and clinical presentation of human osteosarcomas. Currently, serum biomarkers play an important role as sensitive tools for monitoring the cancer development and progression. Each biomarker represents a specific pathogenesis and has different predictive capability. In order to identify their characteristics in human osteosarcoma, multiple potential biomarkers were analyzed simultaneously with clinical presentations.Blood samples were collected from 28 osteosarcoma patients and 30 healthy matched controls. Specific clinical presentations were recorded, including: tumor volume, estimated based on three-dimensional MRI volumetric measurement; metastasis status; and histological cell types. Serum biomarkers analyzed by ELISA-based assays were bone-specific alkaline phosphatase (BALP), vascular endothelial growth factor (VEGF), hyaluronic acid (HA) and chondroitin sulfate WF6 (WF6). Serum lactate dehydrogenase (LDH) was analyzed by a photometric-based system.Serum BALP, LDH and WF6 levels of osteosarcoma patients were significantly higher than those of healthy controls, whereas HA and VEGF levels were not significantly different between the two groups. Serum BALP and LDH were positively correlated with tumor volume, (correlation coefficients 0.5 and 0.4, respectively). Serum BALP from metastasis and osteoblastic subtype group had a significantly higher level than that found in non-metastasis and non-osteoblastic subtypes group, respectively. Upon multivariate analysis, tumor volume was the only factor which correlated with BALP levels.Of the biomarkers analyzed in this study, serum BALP was the most reliable and sensitive for estimating tumor volume. A high level of serum WF6 reflects alteration of the extracellular matrix component of tumors. Both serum biomarkers can be expected to be further explored for use in specific clinical monitoring.