Her-2/neu, p-53, and their coexpression in osteosarcoma. There is controversy regarding the patterns and prognostic significance of Her-2/neu and p-53 expression in osteosarcoma. Further, their combined expression has not been studied.Prechemotherapy biopsy specimens of 63 osteosarcoma patients from June 2004 to August 2006 were analyzed for Her-2/neu and p-53 using immunohistochemistry and compared with grade, stage, and morphologic subtype of tumor.There were 59 high-grade tumors; 32 of 63 had metastases. Histopathologic types included 36 of 63 osteoblastic and 18 of 63 chondroblastic subtypes. Male sex (P=0.045) and chondroblastic type (P=0.004) were associated with metastatic disease. Her-2/neu cytoplasmic staining was seen in 30 of 63 (47.1%) cases, 4 of 30 had additional membranous staining, 17 of 30 were metastatic, and 29 of 30 were high-grade tumors. Staining grade was 3+ in 10 of 30 samples whereas staining intensity 3+ was observed in 26 of 30 samples. Her-2/neu 3+ staining grade was significantly associated with chondroblastic subtype (6/18, P=0.026). P-53 staining was seen in 20 of 63 (31.74%) cases (all high grade), of which 11 were metastatic. Staining grades 3+ and 4+ were seen in 16 of 20 samples whereas staining intensity 3+ in 13 of 20 samples. P-53 expression was higher in chondroblastic (7/18, P value was not significant) and fibroblastic (3/3, P<0.05) subtypes. Coexpression of Her-2/neu and p-53 was seen in 10 cases (15.87%); 3 of 10 cases showed Her-2/neu membranous staining (P=0.01).Her-2/neu (47.1%), p-53 (31.74%), and their combined expression (15.87%) were not related to grade or stage of tumor. Chondroblastic subtype was associated with staining grade 3+ of Her-2/neu staining whereas coexpression of Her-2/neu and p-53 was significantly associated with membranous Her-2/neu staining.