C-erbB-2 expression and prognostic significance in osteosarcoma. C-erbB-2 is postulated as a prognostic biological marker for osteosarcoma (OST). We investigated c-erbB-2 expression status in osteosarcomas and its prognostic significance.Archival pre-treatment tumor biopsies of 79 cases were stained by immunohistochemical (IHC) methods with CB11 antibody for cell-membrane specific c-erbB-2 expression. Relation with different variables was examined and survival rates were calculated.Median age was 13 years (7-17). Distant metastases were detected in 8 (10.1%) cases at initial diagnosis. 36/79 (45.6%) patients had positive c-erbB-2 staining by IHC. There was no significant difference between c-erbB-2 expression and presence of distant metastases at initial diagnosis or during follow-up, gender, age groups, tumor size, tumor sites, serum alkaline phosphatase, and lactate dehydrogenase levels. At a median follow-up of 67.4 months (9.2-246.1), 36 cases died, 20 were alive, and 23 abandoned treatment. For 58 cases without initial metastases who underwent definitive surgery, 5-year event-free (EFS) and overall survival (OS) rates were 50% and 62.1% in cases negative for c-erbB-2 expression, and 22.4% and 32.3% in cases positive for c-erbB-2 expression, respectively (EFS, P = 0.044; OS, P = 0.029). Five-year EFS and OS rates were significantly higher in cases with a tumor size <10 cm. Cox regression analyses revealed that only size persisted as a prognostic factor for EFS. C-erbB-2 expression status didn't appear as an independent prognostic factor.Overexpression of c-erbB-2 in OST was not correlated with metastatic potential. No independent prognostic significance was detected. The results do not support directed therapies for c-erbB-2 in OST.