Periosteal osteosarcoma and parosteal chondrosarcoma evaluated by double immunohistochemical staining. Report of 2 cases. Differentiation of periosteal osteosarcoma and parosteal (periosteal) chondrosarcoma by conventional histology may be difficult. One case each of clinically and histologically proven periosteal osteosarcoma and parosteal chondrosarcoma were evaluated by a double-immunohistochemical staining method using proliferating cell nuclear antigen (PCNA) and S-100 protein (S-100). Conventional histology showed proliferation of both osteoblastic and chondroblastic cells in the periosteal osteosarcoma, while there was a growth of only chondroblastic tumor cells in the parosteal chondrosarcoma. Immunohistochemical studies indicated that the nuclei of chondroblastic cells recognized by S-100 were PCNA-negative, while osteoblastic stromal cells were PCNA-positive in the periosteal osteosarcoma. In contrast, chondroblastic cells in the parosteal chondrosarcoma were both S-100- and PCNA-positive. Our findings suggest that periosteal osteosarcoma is characterized by the proliferation of osteoblastic stromal cells, whereas parosteal chondrosarcoma is characterized by the proliferation of chondroblastic cells. This method of double immunohistochemical staining, using PCNA and S-100, may be useful in differentiating these chondroblastic tumors.