Prognostic significance of serum alkaline phosphatase measurements in patients with osteosarcoma treated with adjuvant or neoadjuvant chemotherapy. It is known that many patients with osteosarcoma have high serum alkaline phosphatase (SAP) levels. The prognostic significance of this finding, however, is still controversial.The pretreatment SAP levels of 656 patients with osteosarcoma of the extremities (107 metastatic and 549 localized at presentation) were examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease.The percentage of patients with increased SAP levels was significantly higher in the metastatic group than in the group of patients with localized disease (91.5% versus 61.3%; P < 0.001). In the latter group, treated with adjuvant and neoadjuvant chemotherapy, the relapse rate was significantly higher in patients with elevated pretreatment SAP levels than in those with normal levels (55.1% versus 26.4%; P < 0.001). Among patients with elevated SAP levels, the percentage of relapses was higher in patients with high levels of the enzyme in comparison with patients with moderately elevated values (66.4% versus 47%; P < 0.05). After treatment, SAP levels almost always return to normal values, and a correlation between postoperative levels of the enzyme and prognosis could not be made.These data demonstrate that in osteosarcoma of the extremities, pretreatment SAP levels have a prognostic value and they should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.