Mutations in the p53 tumor suppressor gene occur in >50% of human malignancies, but are exceedingly rare in benign tumors. The malignant potential of fibrous tumors of children may be unpredictable at microscopic examination. We therefore sought to determine whether malignant fibrous tumors could be distinguished from their benign counterparts by the presence of mutations in p53. We screened 27 fibrous tumor samples from 20 young patients. Tumors were classified as benign, borderline, or malignant by conventional microscopic criteria. RNA extracted from each specimen was used as the template for reverse transcription followed by polymerase chain reaction (PCR) amplification, with six pairs of primers covering the whole coding region of the p53 gene. All PCR products were screened for the presence of mutations using single-strand conformation polymorphism analysis. In addition. PCR products encompassing exons 5–9. the sites of the most frequent mutations in human tumors, were sequenced directly. Both methods detected a single point mutation in a highly malignant tumor (malignant fibrous histiocytoma). The mutation was a silent one at codon 36 (CCG-CCA, Pro-Pro). We conclude that p53 mutations are infrequent in childhood fibrous tumors. consistent with previous observations of low malignant potential (<10%) and better prognosis in this tumor group. Therefore, screening for p53 mutations is not a useful prognostic indicator in fibrous tumors with borderline pattern at microscopic examination.