Previous studies have shown that low levels of p27 KIP1, an inhibitor of G1 cyclin-dependent kinases (CDK), are associated with high aggressiveness and poor prognosis in a variety of cancers. Decreased levels of p27 KIP1 are caused, at least in part, by an acceleration of degradation with Skp2 (S-phase kinase-associated protein 2) and Jab1 (Jun activation domain-binding protein 1). This investigation was undertaken to examine whether the Skp2 and Jab1 expression is correlated with p27 KIP1 protein levels, and how it is clinically relevant in oral squamous cell carcinoma (OSCC). The correlations between p27 KIP1 and Skp2, and p27 KIP1 and Jab1 expression were evaluated by Western blot analysis. Immunohistochemical analysis was done in 75 cases of OSCC. A strongly significant inverse correlation was found between levels of p27 KIP1 and Skp2, and p27 KIP1 and Jab1 (p< 0.0001). Thus, decreased levels of p27 KIP1 were associated with strongly increased levels of Skp2 and Jab1, whereas high levels of p27 KIP1 coincided with low levels of Skp2 and Jab1. Reductions of p27 KIP1 expression and overexpression of Skp2 and Jab1 were significantly associated with cervical lymph node metastasis and poor prognosis. Overexpression of Skp2 and Jab1 is associated with the reduction of p27 KIP1 expression, and may have a role in the progression of OSCC.