To examine the expression of c-Met, c-Erb-b2 (HER2/neu), and epidermal growth factor (EGFR) in a cohort of 12 chordomas, based on the current and future availability of targeted molecular inhibitors. Protein expression levels were analyzed by immunohistochemical analysis from archival tissue using multitumored tissue microarray and by Spearman rank correlation test. Tertiary care facility. We assembled the cohort of 12 chordomas from patients treated at the Yale-New Haven Hospital from 1986 to 2003 and compared them with 51 other tumors from 17 assorted solid tissue tumor types along with 1 sample of healthy tissue from each site. The expression of c-Met, HER2/neu, and EGFR. Most chordomas displayed strong expression of EGFR and c-Met, whereas a variable level of expression of HER2/neu was seen. In addition, we noted a strong correlation between EGFR and c-Met expression, especially for primary chordomas (P = .006). Chordomas, like many other solid-tissue tumors, express HER2/neu, EGFR, and the hepatocyte growth factor/scatter factor receptor c-Met. Most chordomas had strong expression of both the hepatocyte growth factor/scatter factor receptor and EGFR. Inhibitors to EGFR are already in clinical use for other solid-tissue tumors and represent a potentially viable experimental treatment option for refractory chordoma. Further studies are required to investigate these findings.