Epidermal growth factor (EGF) is a potent mitogenic factor for cells of mesodermal and ectodermal origin, and its over-expression is associated with a variety of cancers. We asked whether oncogene coexpression occurs in mesenchymal neoplasms, if coexpression correlates with EGF transcription, and whether coexpression can be attributed to the EGF-induced overexpression of oncogenes. We quantified the mRNA concentrations of EGF and 14 oncogenes in 42 primary sarcomas, 31 benign tumors, and 10 skeletal muscle controls, and compared mRNA concentrations and gene pair correlations in EGF positive (EGF+) tumors to transcript concentrations and correlations in EGF negative (EGF-) tumors. Transcripts were detected by real time reverse transcription-polymerase chain reaction. Pearson's correlation coefficients identified gene associations, and gene synchrony associated with EGF expression was evaluated using chi square. Transcript concentrations in tumors were compared graphically and with t tests. Gene correlations predominated in EGF+ benign tumors and in EGF- primary sarcomas. The dichotomy in oncogene coexpression evident in benign and malignant tumors could not be attributed to statistical differences in mRNA content between EGF+ and EGF- tumors. EGF may enhance, or may indicate the presence of, oncogene coexpression in benign mesenchymal lesions, but counters gene synchronization in sarcomas.