OBJECTIVE: We aimed to characterize the expression of transforming growth factor-a (TGF-alpha) and Ki-67 and to assess the relationship between TGF-alpha and Ki-67 expression and prognostic factors in skull base chordoma. METHODS: We retrospectively analyzed the data from 46 patients with skull base chordoma. The follow-up duration ranged from 1 to 168 months (mean, 74.1). The survival data were statistically analyzed using the Kaplan-Meier method and multivariate Cox regression analysis. The expression of TGF-alpha and Ki-67 were detected by immunohistochemical staining of paraffin-embedded patient tissue specimens. RESULTS: The total resection (TR) group had longer overall survival compared with the non-TR group (P = 0.042). The TR group also had longer progression-free survival (PFS) than did the non-TR group (P = 0.046). The group with a high Ki-67 labeling index (Ki-67LI) had shorter overall survival than did the group with a low Ki-67LI (P = 0.039). Also, the group with a high Ki-67LI had significantly shorter PFS than did the group with a low Ki-67LI (P = 0.016). Moreover, the group with high TGF-alpha expression had significantly shorter PFS compared with the group with low TGF-alpha expression (P = 0.005). CONCLUSIONS: Our results have shown that high levels of TGF-alpha and Ki-67 are associated with shorter PFS in patients with chordoma. We have confirmed the role of Ki-67 as a functional molecular marker of poor prognosis. We also identified TGF-alpha as a potential novel biomarker for predicting prognosis for patients with skull base chordoma.