Expression of CD44 has been identified as a prognostic factor in several malignant diseases. Few studies have correlated CD44 expression in soft tissue sarcoma with subsequent tumor progression or recurrence. We sought to investigate the clinical significance of CD44s (standard) in adult soft tissue sarcoma (STS). Tumor specimens of 62 patients with STS were evaluated by immunohistochemistry for CD44s expression. The primary outcome measures were survival and local recurrence. Of 62 analyzed specimens, 49 tumors were CD44s-positive compared to 13 CD44s-negative tumors. Kaplan-Meier survival analysis indicated significantly better survival among patients whose tumor was CD44s-positive (p=0.015). CD44s expression (hazard ratio, 3.1; 95% confidence interval, 1.5 to 7.0), tumor size (hazard ratio, 11.7; 95% confidence interval, 1.8 to 322) and resection quality (R1 vs. R0: hazard ratio, 8.7; 95% confidence interval, 3.1 to 24.5) were independent predictors of survival in multivariate analysis. CD44s expression correlates with prognosis of soft tissue sarcomas and therefore may have a pathogenetic role in tumor progression. Our results suggest that expression of CD44s in primary STS provides value regarding the progression of STS and, therefore, could be useful in selecting patients for adjuvant treatment.