Forkhead box M1 (FoxM1) transcription factor has been shown to play important roles in regulating the expression of genes that are involved in cell proliferation, differentiation, and transformation by promoting both G(1)/S and G(2)/M transition. Although it has been reported that the FoxM1 signaling network is frequently deregulated with an up-regulated FoxM1 expression in human malignancies, the role of FoxM1 in lung cancer remains to be determined. We performed immunohistochemical detection of FoxM1 protein in 69 tissue samples from patients with primary pulmonary squamous cell carcinoma using a tissue microarray, and Western blotting was done to confirm the immunohistochemical observations. FoxM1 immunoreactivity was observed in 26 (37.7%) of the 69 squamous cell carcinoma cases. Analysis of the FoxM1 expression in 12 squamous cell carcinoma tissues and 2 normal lung tissues by Western blotting confirmed the immunohistochemical results. A FoxM1 expression was more frequently detected in the moderately or poorly differentiated squamous cell carcinomas than in the well-differentiated squamous cell carcinomas (P = .008). The tumors with a positive FoxM1 expression more frequently showed lymph node metastasis (P = .027) and an advanced American Joint Committee on Cancer stage (P = .049). The Kaplan-Meier survival curves demonstrated that patients with a positive FoxM1 expression had a significantly shorter survival time than those patients with a negative FoxM1 expression (P = .003). The multivariate analysis revealed that the FoxM1 expression was an independent poor prognostic factor (P = .018). A subset of pulmonary squamous cell carcinoma with a FoxM1 expression was associated with progressive pathologic features and an aggressive clinical course.