The aim of the present study was to examine the prognostic significance of p27(Kip1) and cyclin E expression in patients with spindle-cell soft tissue sarcomas. In 46 cases of spindle-cell sarcoma including 17 pre-operative biopsy materials, the expression of p27(Kip1) and cyclin E was immunohistochemically examined. The expression of p27(Kip1) decreased in the nuclei of metastatic primary tumor cells (stage IV), whereas the expression of cyclin E increased in those lesions. On univariate analysis, when the expression of p27(Kip1) and cyclin E was analyzed together, patients with spindle-cell sarcoma exhibiting low expression of p27(Kip1) and high expression of cyclin E showed lower distant-metastasis-free survival (DMFS) and overall survival (OS) than those with other combinations of the two parameters (both P < 0.0001). Multivariate analysis revealed that patients with low p27(Kip1) and high cyclin E expression also showed a decrease in DMFS (P = 0.0007, relative risk = 21.3) and OS (P = 0.005, relative risk = 20.8). These results suggest that the combination analysis of p27(Kip1) and cyclin E expression even in biopsy specimens allows the prediction of the clinical behavior of spindle-cell sarcoma.