Forty-two cases of Ewing's sarcoma (ES) have been studied with light microscopy during the 9-year period 1974 to 1982. Thirty-three patients had ES of bone, and in 9 patients the tumor was located in the extraskeletal soft tissues. Cases which fulfilled all the morphologic criteria were accepted as typical ES (31 cases), and those with some architectural or cytologic peculiarities were considered atypical forms of ES (11 cases). An immunohistochemical study (PAP method) to evaluate the presence in the tumor cells of the following markers: myoglobin, F-VIII-related antigen, lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and immunoglobulins (IgG, IgA, IgM, kappa and lambda light chains), was performed with negative results in all cases (paraffin blocks were available in 38 cases). The cytochemical study on fresh tissue imprints from five patients (PAS, Sudan Black, alpha-naphthyl acetate esterase, acid phosphatase, beta glucuronidase, myeloperoxidases, naphthol-AS-D chloroacetate esterase and alkaline phosphatase) gave no pattern of histogenetic significance, PAS being the best morphologic marker in tissue sections and touch preparations. A detailed ultrastructural study was performed on 34 cases; the main findings may be summarized as follows: medium sized cells, polygonal shape, oval nuclei, smooth nuclear envelope, abundant euchromatin, well-developed nucleolonema, scant membranous organelles, abundant hyaloplasmic glycogen, occasional lipid vacuoles, straight cell membranes, and primitive intercellular junctions. No differences were found between bone and extraskeletal ES; moreover, typical and atypical forms showed moderate quantitative differences with no qualitative change. The histogenesis is discussed; no functional or morphologic markers have been found to suggest the cell of origin; however, some cell lines may be excluded. It is the impression of the authors that they are dealing with a primitive noncommitted mesenchymal cell.