The accumulation of mast cells around tumors is a well-recognized phenomenon in a number of malignancies, including basal cell carcinoma, melanoma, and breast cancer. However, little information exists regarding mast cells within tumor nests. To clarify the role of mast cells infiltrating in skin cancers, we examined the morphological features of mast cells within tumors of five cases of angiosarcoma, including two patients with Stewart-Treves syndrome, by electron microscopy. In light microscopy, mast cells were observed within tumor nests at various densities and exhibited weak staining intensity with toluidine blue. By electron microscopy, most of the tumor-infiltrating mast cells exhibited anaphylactic or piecemeal degranulation, indicating that the mast cells had been activated in situ. Some mast cells were noted in close apposition to tumor cells, suggesting the existence of direct cell-to-cell interactions. Tumor cells adjacent to mast cells showed no degenerative changes. In conclusion, these results suggest that careful histologic examination in combination with electron microscopy should enable us to identify more mast cells within cancer lesions with greater sensitivity than in a number of prior reports. Furthermore, the close proximity of mast cells and surrounding tumor cells suggests some biologically significant role of mast cells in the development of angiosarcoma, including tumor growth as well as host immunity and stromal reaction.