Context.-The differential diagnosis of gastrointestinal stromal tumors (GIST) and solitary fibrous tumors (SIFT) may be a diagnostic challenging because of overlapping clinicopathologic features. Many studies have shown consistent immunoreactivity for CD117 (c-Kit) in GIST. However, only a few studies have evaluated CD117 expression in SIFT, and these studies have used an antibody from Santa Cruz Biotechnology. In non-GIST lesions, reactivity with this antibody has been shown to differ from that with a CD117 antibody from Dako Corporation. The immunoreactivity of SFT with the Dako CD117 antibody has not been reported. Conversely, CD99 is a marker for SFT, and its expression in GIST has not been evaluated. Objective.-To study the immunohistochemical profiles of GIST and SFT to evaluate their diagnostic overlap. Design.-We studied the immunoreactivity of 27 unequivocal GIST and 19 unequivocal extra-abdominal SIFT for CD117, CD34, CD99, alpha-smooth muscle actin, vimentin, CD31, S100 protein, and muscle-specific actin. All antibodies, including CD117, were from Dako Corporation. Results.-We found positive immunoreactivity for CD117 in 100% of GIST and none of SFT; for CD34 in 89% of GIST, and 100% of SIFT, for CD99 in 89% of GIST and 100% of SFT; for alpha-smooth muscle actin in 48% of GIST and 31% of SFT, for vimentin in 89% of GIST and 90% of SFT; and for muscle-specific actin in 22% of GIST and none of SIFT. None of the GIST or SFT showed immunoreactivity for CD31 and S100 protein. Conclusions.-The major difference between GIST and SIFT was strong CD117 immunoexpression in all GIST and an absence of this expression in all SFT. With the exception of muscle-specific actin, the prevalence of immunoreactivity for the markers studied did not differ substantially between these 2 tumors. We conclude that GIST and SFT show distinctly divergent immunoprofiles with respect to CD117 and muscle-specific actin.