BACKGROUND: Primary subcutaneous leiomyosarcoma is a rare neoplasm composed of plump, elongated spindle cells arranged in interweaving fascicles. OBJECTIVE: Differential diagnosis might be facilitated by the use of immunohistochemistry. METHODS: A case of subcutaneous leiomyosarcoma was investigated histologically on paraffin-embedded tissue and immunohistochemistry was performed following standard procedures. RESULTS: The case reported exhibited light microscopic features and an immunophenotype characteristic of leiomyosarcoma. However, the intermediate filament desmin could only be found on a small number of tumor cells. CONCLUSION: Expression of these markers might vary considerably and immunoperoxidase stainings need to be carefully evaluated. Utilization of several antibodies directed against different desmin epitopes might be advantageous.