Invasion pathogenesis is one of the most complicated issues in the literature. There are numerous studies concerning the tumor markers implicated in the preinvasive-invasive tumor sequence. Despite ample studies on the invasion pathogenesis of cutaneous melanomas, there is limited and dispersed work presently available on non-melanoma skin cancer. The vast knowledge in the literature concerning this issue in squamous cell carcinoma comes mostly from the studies of the oral cavity, esophagus, larynx, and cervix. In this study, we investigated tumor-free neighboring stroma and tumor stroma in squamous cell carcinomas (SCCs) of the skin as well as keratoacanthomas (KAs) with respect to the presence of stromal CD34-positive (CD34+) fibrocytes and alpha-smooth muscle actin-positive (alpha-SMA+) myofibroblasts using seborrheic keratosis (SKs) and non-tumoral skin samples as controls. We also evaluated the stromal expression pattern of CD26/DPPIV (CD26), a tumor suppressor gene product that also has immunoregulatory properties. Immunohistochemistry was performed on samples of 31 SCC, 8 KA, 15 SK and 10 non-tumoral skin samples. Peri-tumoral stroma from resection margins was also evaluated. We found that CD34 and alpha-SMA demonstrated significantly different staining between benign and malignant squamous skin lesions consisting of a loss of CD34+ fibrocytes paralleled by a gain of alpha-SMA+ myofibroblasts in malignant tumor stroma. Additionally, it was shown that CD26 expression was lower in tumor stroma when compared to that of tumor neighboring stroma. However, we concluded that this finding may be attributable to the solar elastosis areas in the peritumoral tissue, which shows diffuse strong positivity for this marker.