It has been hypothesized that the ability for neoplastic growth of epithelial-derived neoplasms depends upon the stroma. There are currently some studies which show that the stroma surrounding basal cell carcinomas (BCC) is derived from the tumor. In contrast, other studies provide evidence that the stroma is a host-derived response to the tumor. In order to further examine the nature of stroma enveloping cutaneous epithelial neoplasms, we examined a series of tumors which contain abundant stroma, including morpheic type BCC (MBCC), desmoplastic trichoepitheliomas (DTE), and microcystic adnexal carcinomas (MAC). The spindle-shaped cells surrounding the epithelial islands of the two malignant tumors, MBCCs and MACs, were negative in 70% and 100% of cases, respectively, for CD34. In contrast, the spindle-shaped cells surrounding the islands of the benign DTEs were positive for CD34 in 80% of cases. The results suggest that whereas stromal cells surrounding DTEs resemble the CD34-positive perifollicular cells, the spindle-shaped stromal cells surrounding MBCC and MAC are CD34 negative, and may be derived from sources other than the normal mesenchymal tissue surrounding cutaneous appendages.