To investigate the expression of p16, cyclin D1, retinoblastoma tumor suppressor protein (Rb) and MIB-1 in skull base chordoma and chondrosarcoma tissues, and to determine the clinicopathological significance of the above indexes in these diseases. A total of 100 skull base chordoma, 30 chondrosarcoma, and 20 normal cartilage tissue samples were analyzed by immunohistochemistry. The expression levels of p16, cyclinD1, Rb and MIB-1 proteins were assessed for potential correlation with the clinicopathological features. As compared to normal cartilage specimen (control), there was decreased expression of p16, and increased expression of cyclin D1, Rb and MIB-1 proteins, in both skull base chordoma and chondrosarcoma specimens. MIB-1 LI levels were significantly increased in skull base chordoma specimens with negative expression of p16, and positive expression of cyclin D1 and Rb (P < 0.05). Significantly elevated MIB-1 LI was also detected in skull base chondrosarcoma tissues, while there was negative expression of p16, cyclin D1 and Rb (P < 0.05). In skull base chordoma, p16 negatively correlated with cyclin D1 and Rb, while cyclin D1 positively correlated with Rb. Additionally, p16, cyclin D1, Rb, or MIB-1 expression showed no correlation with age, gender, or pathological classification of patients with skull base chordoma (P > 0.05). However, p16 and MIB-1 levels correlated with the intradural invasion, and expression of p16, Rb and MIB-1 correlated with the number of tumor foci (P < 0.05). Further, the expression of p16 and MIB-1 appeared to correlate with the prognosis of patients with skull base chordoma. The abnormal expression of p16, cyclin D1 and Rb proteins might be associated with the tumorigenesis of skull base chordoma and chondrosarcoma.