The histogenetic relationship amongst various dendritic cells of the dermis which may express markers including factor XIIIa (FXIIIa) or CD34 remains unclear. In this study we utilized a sensitive indirect immunoperoxidase staining technique to identify CD34 and FXIIIa, as well the monocyte/macrophage markers KP-1 and MAC 387 expression in a variety of cutaneous dermal tumors of mesenchymal origin to see if differentia] expression of CD34 vs FXIIIa exists. Tumors studied included dermatofibroma (DF) (N = 10), keloid (N=9), atypical fibroxanthoma (AFX) (N = 3), and dermatofibrosarcoma protuberans (DFSP) (N = 7). DF were all composed of FXIIIa + spindle-shaped and stellate tumor cells (mean score = 4.9 or ≥ 75% FXIIIa +) as previously reported, but these cells rarely (< 10%) expressed CD34. Six of 7 DFSP were found to be > 75% CD34+ and FXIIIa negative, while one DFSP was negative for both CD34 and FXIIIa. In all DFSP, there were trapped FXIIIa+ cells which were distinct from the spindle-shaped tumor cells. AFX showed sparse populations of FXIIIa + cells in the stroma (mean score = 1.33 or 10–25% positive), which were distinct from the atypical giant cells characteristic of these tumors. Keloid similarly contained trapped FXIIIa+ cells (mean score = 0.44 or < 5% positive) that were distinct from the spindle-shaped fibroblasts of the tumor mass. Dendritic and spindle-shaped cells within these tumors were consistently both KP-1 and Mac-387 negative, while all lesions studied were characterized by scattered round, histiocytic cells which were KP-1 + and/or Mac-387 + irrespective of tumor cell type. We suggest that these tumors can be delineated by their relative degrees of FXIIIa and CD34 expression and that these neoplasms may be a useful link with which to study the relationship between CD34+ cells and dermal dendrocytes.