Abstract: Only one description of trichoblastic sarcoma exists in the literature. Here, we present the first case of trichoblastic sarcoma with heterologous osteosarcomatous differentiation. Biospy 1 demonstrated an intermediate-grade trichoblastic sarcoma with pleomorphic cells and atypical mitotic figures observed only in the stroma. The epithelium contained no malignant cells. The histologic morphology was reminiscent of an intermediate-grade phyllodes tumor of the breast. Biopsy 2, an excisional biopsy taken 7 months later, showed a high-grade sarcoma with osteosarcomatous differentiation. Immunohistochemistry performed on both specimens showed positive CD10 and bcl-2 staining in the sarcomatous component; p63 was positive in the benign epithelium only. p53 was negative in both the benign epithelium and the malignant stroma. Ki-67 labeling was approximately 10% in both components. Specimen 3, a complete rhinectomy performed 3 months later, showed a poorly differentiated sarcoma. Six months following his rhinectomy procedure, multiple pulmonary nodules consistent with metastatic disease were detected on chest computed tomography. This is the first case report documenting the evolution of an intermediate-grade trichoblastic sarcoma to a high-grade lesion with osteosarcomatous differentiation, to a poorly differentiated sarcoma. The tumor morphologically resembles malignant phyllodes tumor of the breast. Our case is the first to show negative p53 and positive bcl-2 staining in a trichoblastic sarcoma. We propose that cutaneous trichoblastic sarcoma is pathogenetically analogous to phyllodes tumors of the breast, adenosarcoma of the uterus, or ameloblastoma of the oral cavity.