BACKGROUND Determination of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) in urine is a promising method to determine bone resorption. This method is independent of gender, diet and kidney function (creatinine clearance > 25 mL/min). METHODS The diagnostic efficacy of HP and LP was assessed in the urine of adult patients suffering from primary malignant bone tumors (n = 24), bone metastases (n = 38) and soft tissue sarcoma with additional osseous involvement (n = 13). The values were compared with those obtained from 543 healthy controls (aged 15 to 65 years). RESULTS Results clearly exhibited a highly significant increase in HP values (57.75 nmol/mmol creatinine) in adult tumor patients (aged 15 to 65 years) in all three subgroups in comparison with the control group values (22.23 nmol/mmol creatinine) (p = 0.001). Although the LP fraction is more specific for bone than HP, the values of LP from all subgroups of the adult tumor patients were less distinctly but still significantly increased (p = 0.008). Regarding the HP:LP ratio, tumor patients exhibited a markedly increased average molar HP:LP ratio (12.0:1) in comparison to controls (6.6:1). CONCLUSIONS Determination of HP and LP in urine appears to offer clinical utility for the detection of primary and secondary bone neoplasms. Prospective, longitudinal studies will be necessary to evaluate whether the HP:LP ratio is indicative of a relapse of the tumor and consecutively may be adopted in the follow-up of patients with neoplasms.