The focal adhesion kinase (FAK) gene encodes a tyrosine kinase (p125^FAK) thought to be involved in signal transduction pathways used in cell adhesion, motility, and anchorage-independent growth. Because alterations in these cellular processes occur in tumor invasion and metastasis, we studied the protein expression of FAK in a variety of human tumors and found that in the 119 samples studied, increased levels of p125^FAK correlated with the invasive potential of a tumor. By comparing FAK expression in tumors with normal tissue from the same patient, we found that p125^FAK was significantly elevated in 17 (100%) of 17 invasive and metastatic colonic lesions and in 22 (88%) of 25 invasive and metastatic breast tumors. Additional studies of FAK expression in 13 high grade sarcomas showed high levels in all samples compared to benign, noninvasive mesenchymal specimens. Furthermore, FAK protein levels were elevated in preinvasive lesions, such as large (>2 cm) colonic villous adenomas, whereas noninvasive, yet hypercellular, neoplastic tissues such as parathyroid and hepatocellular adenomas did not overexpress FAK. These data provide evidence that both epithelial and mesenchymal tumor progression are accompanied by increased p125^FAK expression and suggest that the level of FAK expression might be a marker for the invasive potential of a tumor.