Melanocytic nevi may microscopically associate with clefts or slits of the nests resembling lymphatic or vascular spaces. This unique histologic feature has been known as an artifact of injection or tissue-processing. We present a case of melanocytic nevus with a prominent vascular space-like structure. We also studied whether intralesional injection of local anesthetic could reproduce similar histologic findings. A 45-year-old Japanese female visited us with a solitary, brownish papule on the chest. Histology revealed numerous nests composed of round to oval-shaped nevus cells throughout the entire dermis. In the mid-dermis, nevus cells were lined up in a layer anastomosing and forming a vascular space-like structure. These nevus cells were uniformly stained with vimentin and S100 protein but not with factor VIII-related antigen. They were also positively immunoreactive with anti-type IV collagen and anti-fibronectin. There were no significant differences in staining intensity in the nevus cells between the solid portion and the vascular space-like structure. In the experimental study, eight melanocytic nevi were removed under local anesthesia. The local anesthetic solution was then injected into the excised nevus. Intralesional injection of a considerable volume of local anesthetic was capable of causing slits or clefts of the nests and dermal edema; however, it failed to reproduce a vascular space-like structure similar to that in the present case. These findings suggest that a vascular space-like structure in melanocytic nevus is not caused by the injection alone. Some other factor(s) may play a major role in the development of such structures in melanocytic nevus.