The co-expression of p53 protein and P-glycoprotein is correlated to a poor prognosis in osteosarcoma. Multidrug resistance (MDR), mediated by P-glycoprotein (P-gp), is an in vitro phenomenon observed within tumour cells, suggesting cross-resistance to unrelated drugs, and expression of P-gp may therefore affect the prognosis and incidence of recurrence after treatment. The mutant p53 protein causes reduced tumour suppression. Co-expression of p53 and P-gp is related to short survival, increased tumour activity and drug resistance. The purpose of this study was to measure the expression of p53 protein and P-gp in osteosarcoma tissue and assess its prognostic significance. Fifty-two tumour specimens were evaluated. The correlation between p53 and P-gp expression was significant (P=0.0008). In univariate analysis of survival, p53 protein was not significant (P=0.2) but P-gp was significant (P=0.0001). The co-expression of p53 and P-gp was the strongest indicator of a short survival according to multivariate analysis (P=0.0004).