Soft tissue swelling represents a common clinical sign of a variety of neoplastic and non-neoplastic lesions. Sarcoma is rarely a cause. Fine needle biopsy as a minimally invasive, economic and accurate method is well suited for the diagnosis of inflammatory/infectious processes as well as of recurrent and metastatic disease. Cytologic diagnosis of primary soft tissue tumors is also feasible. It requires close collaboration with other medical disciplines and incorporation of clinical, radiological and morphologic findings. Clinical data such as age, gender, size and topography are important parameters. The differentiation of cells and properties of the extracellular matrix supplies clues for the differential diagnosis and forms the starting point for immunohistochemical or molecular analysis (FISH, RT-PCR). This analysis may be performed on cytological smears, paraffin embedded material of the cell blocks or on frozen material.