The human hematopoietic progenitor cell antigen is known as CD34. This antigen is present on normal bone marrow progenitor cells and vascular endothelial cells. We used the monoclonal antibody anti-CD34 and immunoperoxidase staining techniques to evaluate the expression of CD34 in benign and malignant vascular and spindle cell tumors. All of the 42 vascular lesions, except two of three lesions of intravascular papillary endothelial hyperplasia, demonstrated diffuse membraneous staining of moderate to strong intensity of their endothelial cells. Also, normal placentas (five) showed similar staining. All neurofibromas (12), three of five neuromas, and one of four neurilemmomas revealed moderate to strong, diffuse, membraneous staining. Five of eight piloleiomyomas, two of seven angioleiomyomas, and one of five uterine leiomyomas showed focal to diffuse, and weak to moderate, membraneous staining in the smooth muscle component. Six dermatofibrosarcoma protuberans were studied: generalized, strongly positive membraneous staining was present in four. All specimens showed staining of the normal endothelial cells and the cells surrounding the hair follicles (bulge area), sebaceous glands, and eccrine glands. No staining was demonstrated in any of the following fibrohistiocytic tumors: atypical fibroxanthomas (two), fibrous dermatofibromas (23), giant cell tumor of tendon sheath (one), and hemosiderotic dermatofibromas (18). Melanocytic tumors [Spitz nevi (three) and spindle cell superficial spreading malignant melanoma (one)], Merkel cell carcinomas (six), and spindle cell squamous cell carcinomas (two) did not stain with anti-CD34. Glomus tumors (two) and a hemangiopericytoma were also negative except for their vascular channels.(ABSTRACT TRUNCATED AT 250 WORDS)