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Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) are small blue cell tumors with no reliable positive diagnostic markers. However, Ewing's sarcoma and PNET recently have been shown to strongly express an antigen determined by the MIC2 gene, whereas other blue cell tumors of childhood for the most part do not.MIC2 analysis therefore offers a distinctive addition to the panel of immunohistochemical stains used to differentiate among small blue cell tumors ofchildhood, since it represents the first positive marker for Ewing's sarcoma andPNET. This study addresses the reliability of MIC2 analysis using the monoclonalantibody 12E7 on tumors registered in the current Intergroup Ewing's Sarcoma protocol. Of 244 tumors, 221 (91%) showed a diffuse strong membranous pattern. The antibody appears to withstand ALL the fixation variables inherent in a multi-institutional study. We conclude that MIC2 expression is highly reliable as a positive marker for the Ewing's sarcoma/PNET family of tumors when the resultsare interpreted in the total context with clinical and pathologic parameters.