Pharmaceutical compositions and methods for treating cancer using CD44 antagonists are disclosed. In certain aspects, these pharmaceutical compositions and methods include treating a mammal having a cancer, such as glioma, colon cancer, breast cancer, prostate cancer, ovarian cancer, lung cancer, renal cell carcinoma, gastric cancer, esophageal cancer, head cancer, neck cancer, pancreatic cancer, or melanoma, with a CD44 fusion protein. These CD44 fusion proteins include CD44-Fc fusions and can be used to detect hyaluronan.