Protooncogenes have the ability to induce and/or maintain the transformed state when they are overly expressed or altered by mutation or gene rearrangement. To study the possible involvement of these cellular oncogenes in the neoplastic transformation, we have analyzed their expression in 44 fresh samples obtained from primary, recurrent, or metastatic tumors from patients with a variety of sarcomas and a melanoma. Our analysis was carried out by the northern blot technique using poly (A)+ RNA hybridized with human cellular DNA probes. A normal 2.3-kb c-myc transcript was observed almost universally at various levels. A normal c-k-ras transcript of 5.2-kb was detected at a low level in most of the samples. In three samples we detected aberrant c-k-ras transcripts of 7.0 and 8.5-kb, while in two other samples we found an aberrant lower-molecular-weight transcript of 1.4-kb. N-myc was expressed in only three samples, and in all instances, the transcripts were aberrant (more than 10-kb). A normal 3.7-kb c-sis transcript was expressed at a low level in most of the sarcomas and the melanoma but was uniquely overexpressed in giant cell tumors of bone. C-fos (2.2-kb) was expressed at a low level in almost half of the samples; c-myb was never expressed. We conclude that c-k-ras, n-myc, c-sis, and c-myc are aberrantly or overexpressed in sarcoma/melanoma, and their activation may play a role in the transforming events leading to development and/or progression of these tumors.